Stable silylating reagents

ABSTRACT

The present disclosure is directed to methods of silylating organic substrates containing C—H or O—H bonds. In some embodiments, the methods use compositions that are derived from the preconditioning of mixtures of hydrosilanes or organodisilanes with bases, including metal hydroxide, metal alkoxide, metal silanoates, potassium amides, and/or graphitic potassium bases.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.15/438,929 filed Feb. 22, 2017 which claims the benefit of priority toU.S. Patent Application Nos. 62/298,337, filed Feb. 22, 2016, and62/361,929, filed Jul. 13, 2016, the contents of which are incorporatedby reference herein for all purposes.

GOVERNMENT RIGHTS

This invention was made with government support under Grant No.CHE1212767 and Grant No. CHE1205646 awarded by the National ScienceFoundation. The government has certain rights in the invention.

TECHNICAL FIELD

This invention is directed to reagents for silylating organicsubstrates.

BACKGROUND

The ability to silylate organic moieties has attracted significantattention in recent years, owing to the utility of the silylatedmaterials in their own rights and as intermediates for other importantmaterials used, for example, in agrichemical, pharmaceutical, andelectronic material applications.

Over the past several decades, considerable effort has been allocated tothe development of powerful catalyst architectures to accomplish avariety of C—H functionalization reactions, revolutionizing the logic ofchemical synthesis and consequently streamlining synthetic chemistry.Accomplishing such challenging transformations can often necessitate theuse of stoichiometric additives, demanding reaction conditions, complexligands, and most notably precious metal catalysts. The need to useprecious metal catalysts for these transformations remains a fundamentaland longstanding limitation.

Recently, systems involving the use of various hydroxides, alkoxides,and other bases have been reported for the silylation of heteroaromatic,alkynyl, alkenyl, and exocyclic C—H bonds and hydroxy O—H bonds usingorganosilanes (a.k.a. hydrosilanes) and organodisilanes. Not reported,however, is the varying induction times which are seen in thesetransformations. Nor has it ever been reported or suggested that stable,storable compositions derived from these bases and silanes can beprepared in advance of contacting the organic substrates and that thesepreconditioned solutions are also operable on these substrates.

The present invention takes advantage of the discoveries cited herein toavoid at least some of the problems associated with previously knownmethods.

SUMMARY

Herein disclosed are chemical compositions and methods employing thesecompositions which eliminate the previously unreported induction times.These compositions, which are stable/storable for up to 6 months orlonger at low temperatures, are prepared by the preconditioning ofmixtures comprising hydrosilanes/organodisilanes and various alkalimetal hydroxides and alkoxides and other bases. Reaction of organicsubstrates, previously shown to be susceptible to silylation with thesecompositions, results in their immediate silylation, i.e., absent anyinduction periods. At least one of the many advantage of thesecompositions is the ability to prepare and store these silylatingagents, without the need to mix and combine all of the ingredients insmall batches, each time they are needed. The catalyticcross-dehydrogenative method avoids the limitations of previousstrategies and successfully couples the appropriate substrates andhydrosilanes.

Various embodiments includes compositions prepared by or preparable bypreconditioning a mixture of:

-   -   (a) a precursor hydrosilane or organodisilane; and    -   (b) a base comprising or consisting essentially of potassium        hydroxide, a potassium alkoxide, a potassium silanolate (e.g.,        KOTMS), rubidium hydroxide, a rubidium alkoxide, a rubidium        silanolate, cesium hydroxide, a cesium alkoxide, a cesium        silanolate, a potassium amide (e.g., potassium        bis(trimethylsilyl) amide), a graphitic potassium (e.g., KC₈),        or a combination thereof;    -   in the substantial absence of a heteroaromatic, olefinic, or        acetylenic substrate capable of C—H silylation,

the preconditioning comprising holding the mixture of the combinedhydrosilane or organodisilane and the base for a time and temperaturesufficient to produce the composition capable of initiating measurablesilylation of 1-methyl indole (N-methylindole) at a temperature of 45°C. (or less) with an induction period of less than 30, 25, 20, 15, 10,5, or 1 minutes. The presence or absence of an induction period may bedetermined using any of the methods described herein for this purpose,for example time-dependent gas chromatography (GC). One exemplarytemperature range to produce such compositions include from about 25° C.to about 125° C. Higher or lower temperatures may also be employed. Oneexemplary temporal range to produce such compositions include from about30 minutes to about 48 hours. Greater or less times may also beemployed, and may be affected by the presence of trace amounts of oxygenor water. That is, while exemplary ranges, it should be appreciated thattimes and temperatures outside these exemplary ranges may also result inthe formation of these compositions.

While the compositions are described in terms of their reactivity withrespect to 1-methyl indole (N-methylindole) (also known as N-methylindole or 1-methyl-1H-indole), the compositions are useful forsilylating a range of other C—H bonds and —OH bonds. The use of 1-methylindole (N-methylindole) is used simply as one standard gauge againstwhich activity is to be measured. It is not meant to be seen as limitingthe composition to applications of this substrate.

Further, these compositions are stable once prepared and may be storedfor up to weeks or months without loss of activity. Exhaustive studieshave been conducted to elucidate the specific nature of the stableingredients of the preconditioned compositions and the mechanisms oftheir action. IR data support the existence of such a hypercoordinatedsilicon species formed, at least, by the hydrosilane and alkoxide,hydroxide or silanolate, and the postulated mechanisms involving suchhypercoordinated silicon hydride anions explain all known observationsmade with respect to these silylating systems.

Other embodiments includes compositions comprising Si—H-based speciesderivable from a preconditioning reaction between:

-   -   (a) a precursor hydrosilane; and    -   (b) a base comprising or consisting essentially of potassium        hydroxide, a potassium alkoxide, a potassium silanolate (e.g.,        KOTMS), rubidium hydroxide, a rubidium alkoxide, a rubidium        silanolate, cesium hydroxide, a cesium alkoxide, a cesium        silanolate, a potassium amide (e.g., potassium        bis(trimethylsilyl) amide, or a combination thereof; again in        the substantial absence of a heteroaromatic, olefinic, or        acetylenic substrate capable of C—H silylation; and        wherein the precursor hydrosilane exhibits an absorption peak in        the Si—H stretching region of infrared spectrum and the        Si—H-based species exhibits an absorption peak in the Si—H        stretching region of an infrared spectrum that is of lower        energy than the absorption peak of the precursor hydrosilane,        when evaluated under comparable conditions.

In some embodiments, Si—H-based species is present in sufficient amountsin the compositions to be characterized by the IR absorbanceattributable to a Si—H stretching frequency, either in solution—e.g.,using ReactI —or as an isolable/isolated solid. While the relativeintensities of these absorption peak attributable to the Si—H stretchingdepend on concentration of these Si—H-based species, and the variousembodiments may be defined in terms of the concentrations of thesespecies (including detectable vs. non-detectable). That is, in someembodiments, the Si—H-based species are present in the compositions atconcentrations sufficient for the IR absorbance attributable to a Si—Hstretching frequency to be present or observed using ReactIR methods.

In various embodiments, compositions are isolable or isolated solids. Inother embodiments, the compositions consist of the precursor hydrosilane(or organodisilane) and an appropriate base (i.e., neat, or withoutextraneous solvent). In still other embodiments, the compositions aresolutions comprising an added solvent—e.g., the reaction solvent used inthe preconditioning. Preferably, the solvent is not measurably reactivewith the Si—H-based species or to the silylation reaction over timescorresponding to storage of use. These solvents may be hydrocarbon- orether-based, preferably an oxygen donor containing solvent, preferablyan ether-type solvent. Ether solvents, such as tetrahydrofurans(including 2-methyl-tetrahydrofuran), diethyl and dimethyl ether,methyl-t-butyl ether, dioxane, and alkyl terminated glycols, such as1,2-dimethoxyethane, have been shown to work well. Polar aproticsolvents including HMPA are also believed to be acceptable. Optionallysubstituted tetrahydrofuran, for example THF or 2 Me-THF (2-methyltetrahydrofuran) are especially preferred for this purpose.

In some cases, the compositions and methods can be derived fromprecursor hydrosilanes of the Formula (I) or Formula (II) ororganosilanes of Formula (III):

(R)_(3−m) Si(H)_(m+1)  (I)

(R)_(3−m)(H)_(m)Si—Si(R)_(2−m)(H)_(m)+₁  (II),

(R′)₃Si—Si(R′)₃  (III)

where m is independently 0, 1, or 2; and each R and R′ are independentlyan optionally substituted alkyl, alkenyl, alkynyl, aryl, and/orheteroaryl moiety, the specifics of which are further describedelsewhere. R′ may also independently comprise optionally substitutedalkoxy, aryloxy, or trimethylsiloxy moieties. In preferred embodiments,the at least one hydrosilane is (R)₃SiH or (R)₂SiH₂, where R isindependently at each occurrence C₁₋₆ alkyl, phenyl, tolyl, orpyridinyl. In some preferred embodiments, the organodisilane ishexamethyldisilane.

In certain preferred embodiments, the base comprises a potassium cationand a hydroxide or a C₁₋₆ alkoxide. Compositions comprising potassiumtert-butoxide are especially preferred.

Some embodiments include a compound, or compositions, comprising thecompound, having an optionally solvated silicon hydride structure ofFormula (IV):

wherein

-   -   M⁺ is or comprises a cation comprising potassium, rubidium,        cesium, or a combination thereof;    -   —OR^(B) is or comprises hydroxide, an alkoxide, an alkyl        silanolate; or a combination thereof; and    -   —R^(S) is or comprises H, —R, or —Si(R)_(3−m)H_(m), or a        combination thereof    -   where m is and R is as described elsewhere herein; or an isomer        thereof.

Additional embodiments of the present invention involve the use of thesecompositions in silylating an organic substrate having an C—H bond or—OH bond, the method comprising contacting the organic substrate with apreconditioned mixture described elsewhere herein wherein the contactingresults in the formation of a C—Si bond or O—Si bond in the positionpreviously occupied by the C—H bond or —OH bond, respectively; and

wherein the C—H bond of the organic substrate is:

(a) located on a heteroaromatic moiety;

(b) located on an alkyl, alkoxy, or alkylene moiety positioned alpha toan aryl or heteroaryl moiety;

(c) an alkynyl C—H bond; or

(d) a terminal olefinic C—H bond;

and wherein the preconditioned mixture is able to initiate [measurable]silylation of 1-methyl indole at a temperature of 45° C. (or less) withan induction period of less than 30, 25, 20, 15, 10, 5, or 1 minutes(each induction period representing an independent embodiment).

Still other embodiments include methods comprising silylating at leastone organic substrate containing a C—H bond or —OH bond, the methodcomprising contacting the organic substrate with:

(a) a precursor hydrosilane; and

(b) a base comprising or consisting essentially of cesium hydroxide,rubidium hydroxide, KC₈, or a combination thereof;

wherein the C—H bond of the organic substrate is:

(a) located on a heteroaromatic moiety;

(b) located on an alkyl, alkoxy, or alkylene moiety positioned alpha toan aryl or heteroaryl moiety;

(c) an alkynyl C—H bond; or

(d) a terminal olefinic C—H bond; and

wherein the contacting results in the formation of a C—Si bond in theposition previously occupied by the C—H bond. These bases have notpreviously been recognized as competent for silylating these organicsubstrates.

In related embodiments, the precursor hydrosilane and the basecomprising or consisting essentially of cesium hydroxide, rubidiumhydroxide, KC₈, or a combination thereof are preconditioned, asdescribed above, before contacting with the organic substrate.

BRIEF DESCRIPTION OF THE DRAWINGS

The file of this patent or application contains at least onedrawing/photograph executed in color. Copies of this patent or patentapplication publication with color drawing(s)/photograph(s) will beprovided by the Office upon request and payment of the necessary fee.The present application is further understood when read in conjunctionwith the appended drawings. For the purpose of illustrating the subjectmatter, there are shown in the drawings exemplary embodiments of thesubject matter; however, the presently disclosed subject matter is notlimited to the specific methods, devices, and systems disclosed. Inaddition, the drawings are not necessarily drawn to scale. In thedrawings:

FIG. 1 illustrates a representative time course of the silylation of1-methylindole (1), monitored by in situ ¹H NMR.

FIG. 2 illustrates the induction period when ingredients mixedsimultaneously and the stability of the preconditioned mixtures for thesilylation of 1-methylindole when applied 2 hours, 24 hours, and 6 weeksafter formation of the preconditioned mixtures

FIG. 3 shows an EPR spectrum taken in THF at 77K at 9.377 GHz, 2.036 mWpower.

FIG. 4 provides a comparison of the kinetic profiles of multiple basecatalysts. Data was acquired via GC analysis of aliquots of crudereaction mixture.

FIG. 5 shows a ReactIR plot of KOt-Bu and Et3SiH in THF. New peakadjacent to Si—H signal of Et₃SiH clearly visible.

FIG. 6 is a representative ReactIR spectrum showing the growth of thenew Si—H peak assigned to the hypercoordinated species, followed byinjection of substrate and immediate product formation.

FIG. 7(A) illustrates the FTIR spectra of Si—H stretching region ofselect metal alkoxides with hydrosilane. Spectra were acquired under anatmosphere of N₂ and are normalized and stacked for clarity. (a) NeatEt₃SiH. (b) Neat KOt-Bu. (c), (d), (e), and (f) Prepared as indicatedwith MOR=KOt-Bu, KOEt, CsOH, and NaOt-Bu, respectively.

FIG. 7(B) is an IR spectrum of pure Et₃SiH.

FIG. 7(C) is an IR spectrum of pure KOt-Bu.

FIG. 7(D) is an IR spectrum of the product of the reaction of KOt-Buwith Et₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removalof volatiles (including Et₃SiH and THF).

FIG. 7(E) is an IR spectrum of the product of the reaction of KOEt withEt₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removal ofvolatiles (including Et₃SiH and THF).

FIG. 7(F) is an IR is an IR spectrum of the product of the reaction ofKOMe with Et₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed byremoval of volatiles (including Et₃SiH and THF).

FIG. 7(G) is an IR spectrum of the product of the reaction of KOTMS withEt₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removal ofvolatiles (including Et₃SiH and THF).

FIG. 7(H) is an IR spectrum of the product of the reaction of KOH withEt₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removal ofvolatiles (including Et₃SiH and THF).

FIG. 7(I) is an IR spectrum of the product of the reaction of RbOH.xH2Owith Et₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removalof volatiles (including Et₃SiH and THF).

FIG. 7(J) is an IR spectrum of the product of the reaction of CsOH.xH2Owith Et₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removalof volatiles (including Et₃SiH and THF).

FIG. 7(K) is an IR spectrum of the product of the reaction of KOt-Buwith Et₃SiD (5 equiv) in THF-D₈ at 45° C. for 2 hours, followed byremoval of volatiles (including Et₃SiH and THF).

FIG. 7(L) is an IR spectrum of the product of the reaction of KOt-Buwith Et₃SiD (2.5 equiv) and Et₃SiH (2.5 equiv) in THF-D₈ at 45° C. for 2hours, followed by removal of volatiles (including Et₃SiH and THF).

FIG. 7(M) is an IR spectrum of the product of the reaction of LiOt-Buwith Et₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removalof volatiles (including Et₃SiH and THF).

FIG. 7(N) is an IR spectrum of the product of the reaction of NaOt-Buwith Et₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removalof volatiles (including Et₃SiH and THF).

FIG. 7(O) is an IR spectrum of the product of the reaction of Mg(Ot-Bu)₂with Et₃SiH (5 equiv) in THF at 45° C. for 2 hours, followed by removalof volatiles (including Et₃SiH and THF).

The file of this patent or application contains at least onedrawing/photograph executed in color. Copies of this patent or patentapplication publication with color drawing(s)/photograph(s) will beprovided by the Office upon request and payment of the necessary fee.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is directed to stable silylation compositions andmethods of using the same. The compositions do not require the presenceof transition metal catalysts, and their ability to silylate heteroaryland other unsaturated substrates does not require their presence or thepresence of UV radiation or electrical (including plasma) discharges.

Methodology for the direct dehydrogenative C—H silylation of heteroarylC—H bonds, acetylenic C—H bonds, and terminal olefinic C—H bonds havepreviously been reported, but these previous methods have been describedonly in terms of the simultaneous or near-simultaneous mixing of theingredients before subjecting them to the reaction conditions. See,e.g., U.S. patent application Ser. No. 14/043,929, filed Oct. 2, 2013(heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167; Ser. No.14/818,417, filed Aug. 5, 2015 (heteroaromatics with hydroxides); Ser.No. 14/841,964 filed Sep. 1, 2015 (alkynes), now U.S. Pat. No.9,556,206; Ser. No. 14/972,653, filed Dec. 17, 2015 (disilanes), nowU.S. Pat. No. 9,556,08; and Ser. No. 15/166,405 (terminal olefins),filed May 27, 2016, each of which is incorporated by reference herein inits entirety for all purposes, but especially for their methods of use,substrate range, and experimental conditions.

While these systems and methods described the use of hydrosilanes ororganodisilanes and bases such as hydroxides, alkoxides, and anionicamides, their underlying mechanisms were undefined. In studies aimed atidentifying the mechanistic bases for these reactions, the presentinventors have identified a series of solution-stable compositionscapable of silylating the same substrates as previously reported. Thesesolution-stable compositions allow for the bulk preparation and storageof the silylating agents, avoiding the need to handle small quantitiesof reactive hydrosilanes on an individual batch basis, and therebysimplifying their use. These compositions may also incorporate highlyvolatile liquid or even gaseous hydrosilanes or organodisilanes intoless volatile solvents, again simplifying handling of these silanereagents. Thirdly, the use of these preconditioned solutions alsoprovides a reactivity that avoids the previously observed inductionperiods associated with the silylation reactions.

The present invention may be understood more readily by reference to thefollowing description taken in connection with the accompanying Figuresand Examples, all of which form a part of this disclosure. It is to beunderstood that this invention is not limited to the specific products,methods, conditions or parameters described or shown herein, and thatthe terminology used herein is for the purpose of describing particularembodiments by way of example only and is not intended to be limiting ofany claimed invention. Similarly, unless specifically otherwise stated,any description as to a possible mechanism or mode of action or reasonfor improvement is meant to be illustrative only, and the inventionherein is not to be constrained by the correctness or incorrectness ofany such suggested mechanism or mode of action or reason forimprovement. Throughout this text, it is recognized that thedescriptions refer to both the compositions and methods of making andusing said compositions. That is, where the disclosure describes orclaims a feature or embodiment associated with a composition or a methodof making or using a composition, it is appreciated that such adescription or claim is intended to extend these features or embodimentto embodiments in each of these contexts (i.e., compositions, methods ofmaking, and methods of using).

Silylating Compositions

Certain embodiments of the present invention include those compositionsprepared by preconditioning a mixture of: (a) a precursor hydrosilane ororganodisilane; and (b) a base comprising or consisting essentially ofpotassium hydroxide, a potassium alkoxide, a potassium silanolate (e.g.,potassium trimethylsilanolate, KOTMS), rubidium hydroxide, a rubidiumalkoxide, a rubidium silanolate, cesium hydroxide, a cesium alkoxide, acesium silanolate, a potassium amide (e.g., potassiumbis(trimethylsilyl) amide), a potassium graphite (e.g., KC₈), or acombination thereof; the preconditioning comprising holding the mixtureof combined hydrosilane and the base under conditions sufficient toproduce the composition capable of initiating measurable silylation of asuitable substrate on contacting the mixture and the substrate after atleast 30 minutes of preconditioning the mixture. The preconditioning mayalso comprise holding the mixture of combined hydrosilane and the baseunder conditions sufficient to silylate 1-methyl indole at a temperatureof 45° C. (or less) with an induction period of less than 30, 25, 20,15, 10, 5, or 1 minutes. The presence or absence of an induction periodmay be determined using any of the methods described herein for thispurpose, for example time-dependent gas chromatography (GC). Oneexemplary temperature range to produce such compositions include fromabout 25° C. to about 125° C. One exemplary temporal range to producesuch compositions include from about 30 minutes to about 24 hours. Whileexemplary ranges, it should be appreciated that times and temperaturesoutside these exemplary ranges may also result in the formation of thesecompositions.

Given the effectiveness of graphitic potassium (e.g., KC₈) in theseapplications, it is also reasonable to expect that potassium depositedon other surfaces (e.g., allotropes of carbons such as graphene,graphene oxide, charcoal, or activated carbon, alumina, or silica) arealso operable, and considered within the scope of the presentdisclosure.

Again, while the compositions are described in terms of their reactivitywith respect to 1-methyl indole (N-methyl indole), the compositions areuseful for silylating a range of other C—H or —OH bond. The use of1-methyl indole (N-methyl indole) is used simply as one standard gaugeagainst which activity is to be measured. It is not meant to be seen aslimiting the composition to applications of this substrate.

While other embodiments may describe these preconditioned compositionsin terms of silicon hydrides, as described elsewhere herein, thispreconditioning reaction may or may not result in the observablepresence of a Si—H-based species. Rather, another measure of thepresence of a persistent, stable silylation reaction is the ability ofthe material to silylate suitable substrates (i.e., previously shown tobe susceptible to silylation when mixed simultaneously with thehydrosilane/base combinations, such as previously reported and describedelsewhere herein), even after cold storage of the Si—H-based species insolution for periods of time in excess of 1 hour, 6 hours, 12 hours, 24hours, a week, two weeks, a month, six months, up to a year or more. SeeFIGS. 1 and 2. At least in this regard, the term “stable” may be alsorefer to “storable.” Even more interesting, these preconditionedcompositions are capable of silylating suitable organic substrates,including heteroaromatic substrates, on immediate or practicallyimmediate contact with these substrates, or shortly thereafter.

While not previously reported, but as described in the present Examples,silylations of heteroaromatic substrates using hydrosilanes and basecatalysts in which the ingredients are simultaneously ornear-simultaneously mixed, such as described in U.S. patent applicationSer. No. 14/043,929, filed Oct. 2, 2013 (heteroaromatics withalkoxides), now U.S. Pat. No. 9,000,167; Ser. No. 14/818,417, filed Aug.5, 2015 (heteroaromatics with hydroxides); Ser. No. 14/841,964 filedSep. 1, 2015 (alkynes), now U.S. Pat. No. 9,556,206; and Ser. No.15/166,405 (terminal olefins), filed May 27, 2016, each of which isincorporated by reference herein, undergo the silylation reactions witha measurable induction period. This feature has not been previouslyreported. Yet, when the hydrosilanes and the bases are preconditioned asdescribed herein, the preconditioned mixtures are stable and thereaction proceeds without any such induction period.

In other embodiments, the preconditioned compositions may becharacterized or described in terms of Si—H-based species, as describedherein. That is, certain other embodiments of the present inventioninclude those compositions comprising a Si—H-based species derivablefrom the preconditioning reaction between: (a) a precursor hydrosilane;and (b) a base comprising or consisting essentially of potassiumhydroxide, a potassium alkoxide, a potassium silanolate (e.g., KOTMS),rubidium hydroxide, a rubidium alkoxide, a rubidium silanolate, cesiumhydroxide, a cesium alkoxide, a cesium silanolate, a potassium amide(e.g., potassium bis(trimethylsilyl) amide), or a combination thereof.In some aspects of these embodiments, the Si—H-based species derived orderivable from the preconditioning reaction may be identified by acharacteristic shift of its infrared Si—H stretching frequency. That is,the precursor hydrosilane exhibits an absorption peak in the Si—Hstretching region of infrared spectrum which depends on the nature ofthe precursor hydrosilane, and the Si—H-based species exhibits anabsorption peak in the Si—H stretching region of an infrared spectrumthat is of lower energy (lower wavenumbers) than the absorption peak ofthe precursor hydrosilane, when evaluated under comparable conditions.Such Si—H-based species can be present and detected in solution, or assolid compositions (see Examples).

In solution, the presence of the product/intermediate Si—H-based speciescan be and has been observed in solution using in situ Fourier TransformInfrared (FTIR) methods. For example, Mettler Toledo makes ReactIRequipment for just such analyses. Suitable for a wide range ofchemistries, ReactIR provides real-time monitoring of key reactionspecies, and how these species change during the course of the reaction.Designed to follow reaction progression, ReactIR Attenuated TotalReflection (ATR) provides specific information about reactioninitiation, conversion, intermediates and endpoint. As shown in theExamples, reactions of the exemplar silane Et₃SiH has been shown toreact with the alkoxides and hydroxides cited herein to providespectroscopically structures consistent with hypercoordinated siliconhydrides.

These Si—H-based species resulting from the preconditioning exhibit IRabsorption shifts, depending on both the hydrosilanes and especiallywith the nature of the alkoxide or hydroxide bases, consistent with therelative reactivities of these hydrosilane/base pairs with organicsubstrates.

It is noted here that, while consistent with such structures and theobservation of such infrared absorptions correlate with silylationreactivities, the claims are not necessarily bound to the correctness orincorrectness of such an interpretation. Stated otherwise, thesepreconditioned compositions may be described or characterized asexhibiting an infrared absorbance peak in a range consistent with, butnot necessarily attributable to, a Si—H stretching frequency; e.g., in arange of from about 2000 to 2100 cm′. And again, these absorbances areof lower energy (at lower wavenumbers) than the precursor silane. Insome embodiments, the absorbance peaks may be shifted to lowerwavenumbers in a range of from 10 to 100 cm-1, or as shown in FIG. 7A.It should be apparent to the skilled artisan, that compositionspreconditioned with deuterosilanes do not exhibit absorbances in thisrange, but do exhibit the reactivities described above.

In various embodiments, the Si—H-based species are present in thepreconditioned composition in amounts sufficient to detect thisabsorption peak attributed to the Si—H stretching region of an infraredspectrum.

In some embodiments, these preconditioned compositions exist assolutions. In other embodiments, they are present solvent-free or asisolated solids or semi-solids. In the former case, then, thesepreconditioned compositions may be described as comprising a solvent,typically an organic solvent, preferably an anhydrous solvent.Preferably such compositions are substantially free of other oxidizingspecies, including air, oxygen, or transition metal compounds orspecies. Also, the solvent is preferably not measurably reactive withthe preconditioned compositions, including the Si—H-based species, or tothe silylation reaction. Suitable solvents include hydrocarbons, such asaromatic hydrocarbons, for example benzene or toluene Other suitable andpreferred solvents include those comprising so-called oxygen donorsolvents, preferably ether-type solvents. Tetrahydrofurans (including2-methyl-tetrahydrofuran), diethyl and dimethyl ether, methyl-t-butylether, dioxane, and alkyl terminated glycols, such as1,2-dimethoxyethane have been shown to work well. Other polar aproticsolvents including hexamethylphosphoramide (HMPA) are also believed tobe acceptable. Tetrahydrofurans, including 2-methyl-tetrahydrofuran),are preferred.

As described above, in some embodiments, the base used in theprecondition reaction comprises potassium hydroxide, rubidium hydroxide,cesium hydroxide, potassium alkoxide, a rubidium alkoxide, or a cesiumalkoxide, or a mixture thereof. Other bases, such as those describedelsewhere herein may also be used. Suitable alkoxides include C₁₋₆alkoxides, such as methoxide, ethoxide, n-propoxide, isopropoxide,n-butoxide, sec-butoxide, tert-butoxide, n-pentoxide, 2-pentoxide3-pentoxide, or iso-pentoxide, preferably tert-butyl butoxide. Of thebases tested thus far, potassium alkoxide, and especially potassiumtert-butoxide is preferred.

Suitable silanolates include those structures of formulae (C₁₋₆alkyl)₃Si—O—, where the C₁₋₆ alkyls are independently placed. KOTMS,potassium trimethylsilanolate, is an attractive silanolate in thisapplication.

In some embodiments, the precursor hydrosilane used in thepreconditioned composition is of the Formula (I) or Formula (II):

(R)_(3−m)Si(H)_(m+1)  (I)

(R)_(3−m)(H)_(m)Si—Si(R)_(2−m)(H)_(m+1)  (II)

where: m is independently 0, 1, or 2; and each R is independentlyoptionally substituted C₁₋₂₄ alkyl or heteroalkyl, optionallysubstituted C₂₋₂₄ alkenyl, optionally substituted C₂₋₂₄ alkynyl,optionally substituted C₆₋₁₂ aryl, C₃₋₁₂ heteroaryl, optionallysubstituted C₇₋₁₃ alkaryl, optionally substituted C₄₋₁₂ heteroalkaryl,optionally substituted C₇₋₁₃ aralkyl, or optionally substituted C₄₋₁₂heteroaralkyl, and, if substituted, the substituents may be phosphonato,phosphoryl, phosphonyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀alkylsulfinyl, 5 to 12 ring-membered arylsulfinyl, sulfonamido, amino,amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy,C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl, carboxylato,mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato, thiocyanato,isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy,silanyl, siloxazanyl, boronato, boryl, or halogen, or a metal-containingor metalloid-containing group, where the metalloid is Sn or Ge, wherethe substituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.

In certain preferred embodiments, the precursor hydrosilane used in thepreconditioned composition is or comprises a compound of formula (R)₃SiHor (R)₂SiH₂, where R is independently at each occurrence C₁₋₆ alkyl,phenyl, tolyl, or pyridinyl. Exemplary precursor hydrosilane includethose were R is independently at each occurrence methyl, ethyl, propyl,butyl, propyl, phenyl, biphenyl, benzyl, or pyridinyl, or substitutedderivatives thereof.

In some embodiments, the precursor organodisilane used in thepreconditioned composition is of the Formula (III):

(R′)₃Si—Si(R′)₃  (III),

where R′ is described above. R′ may additionally independently comprisean optionally substituted C₁₋₂₄ alkoxy, an optionally substituted C₆₋₁₂aryloxy, optionally substituted C₃₋₁₂ heteroaryloxy, optionallysubstituted C₇₋₁₃ alkaryloxy, optionally substituted C₄₋₁₂heteroalkaryloxy, optionally substituted C₆₋₁₂ aralkoxy, C₄₋₁₂heteroaralkoxy or a trimethylsiloxy moiety. In preferred embodiments, R′is independently C₁₋₃ alkyl or aryl; in other preferred embodiments, theorganodisilane is hexamethyldisilane, tetramethyldiphenyldisilane,hexaethoxydisilane, or hexamethoxydisilane.

Accordingly, certain embodiments of the present invention include acompound having an optionally solvated silicon hydride structure ofFormula (IV):

wherein

-   -   M⁺ is or comprises a cation comprising potassium, rubidium,        cesium, or a combination thereof;    -   —OR^(B) is or comprises hydroxide, an alkoxide, an alkyl        silanolate; or a combination thereof; and    -   —R^(S) is or comprises H, —R, or —Si(R)_(3−m)H_(m), or a        combination thereof where m is and R is as described elsewhere        herein; or an isomer thereof.

Alternatively stated, this compound may be described or characterized asthe addition product of (a) potassium hydroxide, a potassium alkoxide, apotassium silanolate, rubidium hydroxide, a rubidium alkoxide, arubidium silanolate, cesium hydroxide, a cesium alkoxide, a cesiumsilanolate, or a combination thereof with (b) a precursor hydrosilane ofFormula (I) or (II), or any of the individual precursor hydrosilanes asdescribed elsewhere herein.

The structure of Formula (IV) is analogous to structures previouslyobserved in other systems, though the present structures exhibitdramatically different and totally unexpected activity. For example, theaddition of strong silicophilic Lewis bases (e.g. fluoride, alkoxide)are known to be able to increase the reactivity of hydrosilanes in thehydrosilylation of C═O bonds. It has been speculated that stronglyreducing hypercoordinate silicate complexes are formed by coordinationof nucleophilic anions during such processes, which typically weakensthe Si—H bond and increases the hydridic character of this bond. Studiesby Corriu et al. revealed that the direct reaction of (RO)₃SiH with thecorresponding KOR (R=alkyl or aryl) in THF at room temperature affordsthe anionic, five-coordinate hydridosilicate [HSi(OR)₄]K in good yield.See, e.g., Becker, B., et al., J. Organometallic Chem., 359 (2), January1989, pp. C33-C35; Corriu, R., et al., J. C. Chem. Rev. 1993, 93,1371-1448; Corriu, R. J., et al., Tetrahedron 1983, 39, 999-1009; Boyer,J.; et al., Tetrahedron 1981, 37, 2165-2171; Corriu, R., et al.,Organometallics 2002, 10, 2297-2303; and Corriu, R., et al., Wang, Q. J.Organomet. Chem. 1989, 365, C7-C10.

As is described elsewhere herein, the compounds having an optionallysolvated structure of Formula (IV) have been characterizedspectroscopically and by their reactivity (in terms of substrate andregioselectivity) and kinetic profiles. The Si—H bond of the compoundhaving an optionally solvated structure of Formula (IV) appears exhibitBrønsted-Lowry basicity. Silicon is less electronegative than hydrogen,and the Si—H bond in (IV) possesses some hydridic character. Uponnucleophilic (tBuO-) attack, the Si—H bond in the hypercoordinatedsilicon intermediate (IV) can, in some circumstances, serve as a hydridedonor. Indeed, cleavage of the Si—H bond in hydrosilanes by strongnucleophiles to form alkylated or arylated silanes with loss of hydrideis precedented in the literature. Therefore, the silane hydrogen in (IV)is expected to be sufficiently basic to abstract a proton fromheteroaromatic substrates leading to formation of H2. This propositionis further supported by an isotope labelling experiment: whenC₂-deuterated 1-methyl indole substrate was used as a substrate, theevolution of HD gas was observed.

Likewise, when different alkoxide bases were used as catalysts instoichiometric reactions, the reaction efficiencies followed roughly thebasicities (i.e., KOtBu>KOEt>KOMe). (alkoxide application). Thisbehavior is consistent with the proposed addition of the alkoxide anionto the silane precursor silane to form the reactive hypercoordinatedsilicon intermediate.

The nature of the cation has previously been described—i.e., thesilylations, at least of heteroarenes, fail to operate with sodium orlithium cations by themselves or when the added potassium ions aresequestered (for example, by crown ethers), but operate with facilitywhen potassium, rubidium, or cesium are used. Interestingly, thesilylation of alkynes or alcohols operate when the bases comprise sodiumcations, and, while hydrides comprising these cations have not beenobserved, the stable preconditioned mixtures may be derived from suchbases. Clearly, the cations play a non-innocent role in the activity ofthese reagents. Without intending to be bound by the correctness of anyparticular theory, perhaps this role involves either the(de)stabilization of the catalytic intermediate or the activation thesubstrate. As such, where the bases are characterized herein ascomprising potassium, rubidium, or cesium hydroxides, alkoxides, orsilanolates are to be used in the absence of crown ethers or othercation sequestering agents. Further, these bases can also be describedas including sources of these unsequestered cations (K⁺, Cs⁺, Rb⁺) withsources the operative hydroxide, alkoxide, or silanolate anions. Forexample, the use LiOH, NaOH, or alkaline earth metal hydroxides in thepresence of added potassium salts, such as potassium chloride, nitrate,sulfate, or of a potassium salt comprising another similar non-reactiveanion, may be considered a functional equivalent to KOH itself.

Under certain conditions, the preconditioned compositions exhibitcharacter consistent with the homolytic scission of the Si—H bond, andthe corresponding formation of a radical species. This may suggest thepotential utility of these compounds or compositions as one-electronreductants, for example of transition metal complexes such as thosecomprising iron or cobalt.

Methods of Use

To this point, the invention has been describe in terms of compositions,but it should be appreciated that the compositions are also useful insilylation methods, and certain embodiments are directed toward theiruse in this capacity.

Some embodiments of the present invention include those where thepreconditioned compositions, and/or the compositions of Formula (IV) arecontacted with an organic substrate having an appropriate C—H bond or anO—H bond to silylate that carbon or oxygen. For example, someembodiments include method comprising contacting the organic substratewith any of the preconditioned mixtures described herein, wherein thecontacting results in the formation of a C—Si bond in the positionpreviously occupied by the C—H bond or in the formation of a O—Si bondin the position previously occupied by the O—H bond;

wherein the C—H bond of the unsaturated substrate is:

(a) located on a heteroaromatic moiety;

(b) located on an alkyl, alkoxy, or alkylene moiety positioned alpha toan aryl or heteroaryl moiety;

(c) an alkynyl C—H bond; or

(d) a terminal olefinic C—H bond.

Each of the permutations of preconditioning conditions, bases,hydrosilanes, and substrates is deemed an independent embodiment of thisdisclosure as if each had been individually cited. In specificindependent embodiments, the preconditioned mixtures and organicsubstrates are placed into contact for times of at least 30 minutes, 1hour, 4 hours, 8 hours, 12 hours, 24 hours, 2 days, 4 days, 7 days, 14days, or 28 days after the preconditioning reaction is done. Typically,especially for the extended periods, the preconditioned mixtures arerefrigerated to favor the stability. Contacting the preconditioningconditions, bases, hydrosilanes, and substrates generally includesholding the resulting mixtures at one or more temperatures in a range offrom about 25° C. to about 75° C. for a time in a range of from about 1hour to about 48 hours, or as described in the various applicationscited herein with respect to the specific organic substrates.

It is further recognized that the use of cesium hydroxide, rubidiumhydroxide, or KC₈ has not been previously recognized or disclosed as acompetent base for silylation reactions in combinations withhydrosilanes and, at least, heteroaromatic substrates. As such, methodsdescribing their use in this capacity are considered independentembodiments of this disclosure. Certain embodiments, then, include thosemethods silylating at least one organic substrate containing a C—H bondor —OH bond, the method comprising contacting the organic substratewith:

-   -   (a) a precursor hydrosilane; and    -   (b) a base comprising or consisting essentially of cesium        hydroxide, rubidium hydroxide, KC₈, or a combination thereof;    -   wherein the C—H bond of the unsaturated substrate is:    -   (a) located on a heteroaromatic moiety;    -   (b) located on an alkyl, alkoxy, or alkylene moiety positioned        alpha to an aryl or heteroaryl moiety;    -   (c) an alkynyl C—H bond; or    -   (d) a terminal olefinic C—H bond; and

wherein the contacting results in the formation of a C—Si bond in theposition previously occupied by the C—H bond.

Still further embodiments include those methods wherein the precursorhydrosilane and the base are preconditioned before contacting with theorganic substrate, the preconditioning comprising holding a mixturecomprising the precursor hydrosilane and the base under conditionssufficient to produce the composition capable of initiating measurablesilylation of a suitable substrate on contacting the mixture and thesubstrate after at least 30 minutes of preconditioning the mixture. Thepreconditioning may also comprise holding the mixture of combinedhydrosilane and the base under conditions sufficient to initiatemeasurable silylation of 1-methyl indole at a temperature of 45° C. (orless) with an induction period of less than 30, 25, 20, 15, 10, 5, or 1minutes.

Substrates Susceptible to Silylations

Previous applications by some of the same inventors have described theuse of base and hydrosilanes to silylate organic substrates having C—Hbonds or —OH bonds, wherein the silylation is defined in terms ofreplacing a C—H bond with C—Si bond or an O—H bond with an O—Si bond.See, for example, U.S. patent application Ser. No. 14/043,929, filedOct. 2, 2013 (heteroaromatics with alkoxides), now U.S. Pat. No.9,000,167; Ser. No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics withhydroxides); Ser. No. 14/841,964 filed Sep. 1, 2015 (alkynes), now U.S.Pat. No. 9,556,206; Ser. No. 15/166,405 (terminal olefins), filed May27, 2016; and Ser. No. 15/219,710, filed Jul. 26, 2016 (alcohols withhydroxides), each of which is incorporated by reference, at least fortheir teaching of methods and reaction conditions, including substratesand reactants relating to silylating their respective substrates.

The methods described herein are appropriately applied to any of thesubstrates described in these patent applications, including thosewherein the organic substrate is or comprises:

(1) a heteroaromatic moiety, for example comprising an optionallysubstituted furan, pyrrole, thiophene, pyrazole, imidazole, triazole,isoxazole, oxazole, thiazole, isothiazole, oxadiazole, pyridine,pyridazine, pyrimidine, pyrazine, triazone, benzofuran, benzothiophene,isobenzofuran, isobenzothiophene, indole, isoindole, indolizine,indazole, azaindole, benzisoxazole, benzoxazole, quinoline,isoquinoline, cinnoline, quinazoline, naphthyridine,2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, ordibenzothiophene moiety. More specific example of these substrates aredescribed in U.S. patent application Ser. No. 14/043,929, filed Oct. 2,2013 (heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167 orSer. No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics withhydroxides), each of which is incorporated by reference herein at leastfor these teachings.

(2) a substrate comprising an alkyl, alkoxy, or alkylene moietypositioned alpha to an aryl or heteroaryl moiety, for example a benzylicC—H bond or a C—H bond which exists alpha to a heteroaryl group, such as1,2 dimethylindole or 2,5-dimethylthiophene, or an exocyclic methoxygroup. More specific example of these substrates are described in U.S.patent application Ser. No. 14/043,929, filed Oct. 2, 2013(heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167 or Ser.No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics with hydroxides).

(3) an alkynyl C—H bond having a formula:

R³—C≡C—H,

where R³ comprises an optionally substituted C₁₋₁₈ alkyl, optionallysubstituted C₂₋₁₈ alkenyl, optionally substituted C₂₋₁₈ alkynyl,optionally substituted C₆₋₁₈ aryl, optionally substituted C₆₋₁₈ aryloxy,optionally substituted C₇₋₁₈ aralkyl, optionally substituted C₇₋₁₈aralkyloxy, optionally substituted C₃₋₁₈ heteroaryl, optionallysubstituted C₃₋₁₈ heteroaryloxy, optionally substituted C₄₋₁₈heteroarylalkyl, optionally substituted C₄₋₁₈ heteroaralkyloxy, oroptionally substituted metallocene. More specific example of thesesubstrates are described in U.S. patent application Ser. No. 14/841,964filed Sep. 1, 2015 (alkynes), now U.S. Pat. No. 9,556,206, which isincorporated by reference herein at least for these teachings.

(4) a terminal olefin has a Formula (V):

where p is 0 or 1; R¹ and R² independently comprises H, an optionallysubstituted C₁₋₁₈ alkyl, optionally substituted C₂₋₁₈ alkenyl,optionally substituted C₂₋₁₈ alkynyl, optionally substituted C₆₋₁₈ aryl,optionally substituted C₁₋₁₈ heteroalkyl, optionally substituted 5-6ring membered heteroaryl, optionally substituted 5-6 ring memberedaralkyl, optionally substituted 5-6 ring membered heteroaralkyl, oroptionally substituted metallocene, provided that R¹ and R² are not bothH. More specific example of these substrates are described in U.S.patent application Ser. No. 15/166,405 (terminal olefins), filed May 27,2016, which is incorporated by reference herein at least for theseteachings.

(5) an organic alcohol, having a structure of Formula (VIA) or (VIB).

R⁴—OH  (VIA)

HO—R⁵—OH  (VIB),

where R⁴ comprises an optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₂₋₂₄ alkenyl, optionally substituted C₂₋₂₄ alkynyl,optionally substituted C₆₋₂₄ aryl, optionally substituted C₁₋₂₄heteroalkyl, optionally substituted 5- or 6-ring membered heteroaryl,optionally substituted C₇₋₂₄ aralkyl, optionally substitutedheteroaralkyl, or optionally substituted metallocene; and where R⁵comprises an optionally substituted C₂₋₁₂ alkylene, optionallysubstituted C₂₋₁₂ alkenylene, optionally substituted C₆₋₂₄ arylene,optionally substituted C₁₋₁₂ heteroalkylene, or an optionallysubstituted 5- or 6-ring membered heteroarylene. In some Aspect of thisEmbodiments, the organic substrate having at least one organic alcoholmoiety is or comprises an optionally substituted catechol moiety or hasa Formula (IV):

wherein n is from 0 to 6, preferably 0 or 1;

R^(M) and R^(N) are independently H or methyl

R^(D), R^(E), R^(F), and R^(G) are independently H, C₁₋₆ alkyl, C₁₋₆alkenyl, optionally substituted phenyl, optionally substituted benzyl,or an optionally substituted 5- or 6-ring membered heteroaryl, whereinthe optional substituents are C₁₋₃ alkyl, C₁₋₃ alkoxy, or halo. Withinthis genus, the organic substrate includes substituted 1,2-diols,1,3-diols, 1,4-diols, these being substituted with one or more alkyland/or optionally substituted aryl or heteroaryl substituents. Theorganic substrate is any one having a terminal olefin as described inU.S. patent application Ser. No. 15/219,710 (alcohols), filed Jul. 26,2016, which is incorporated by reference herein at least for theseteachings.

As shown in the Examples, the present compositions/compounds also appearto be suitable reagents for the deprotection/cleavage of amide groups orother acyl protected functional groups (e.g., esters). While Example 2.7shows the exemplary deprotection of N-benzoylindole, other carbonylprotected amines or alcohols, for example by acetyl (Ac) as well asbenzoyl (Bz) functional groups may be expected to react similarly.

Terms

In the present disclosure the singular forms “a,” “an,” and “the”include the plural reference, and reference to a particular numericalvalue includes at least that particular value, unless the contextclearly indicates otherwise. Thus, for example, a reference to “amaterial” is a reference to at least one of such materials andequivalents thereof known to those skilled in the art.

When a value is expressed as an approximation by use of the descriptor“about,” it will be understood that the particular value forms anotherembodiment. In general, use of the term “about” indicates approximationsthat can vary depending on the desired properties sought to be obtainedby the disclosed subject matter and is to be interpreted in the specificcontext in which it is used, based on its function. The person skilledin the art will be able to interpret this as a matter of routine. Insome cases, the number of significant figures used for a particularvalue may be one non-limiting method of determining the extent of theword “about.” In other cases, the gradations used in a series of valuesmay be used to determine the intended range available to the term“about” for each value. Where present, all ranges are inclusive andcombinable. That is, references to values stated in ranges include everyvalue within that range.

It is to be appreciated that certain features of the invention whichare, for clarity, described herein in the context of separateembodiments, may also be provided in combination in a single embodiment.That is, unless obviously incompatible or specifically excluded, eachindividual embodiment is deemed to be combinable with any otherembodiment(s) and such a combination is considered to be anotherembodiment. Conversely, various features of the invention that are, forbrevity, described in the context of a single embodiment, may also beprovided separately or in any sub-combination. Finally, while anembodiment may be described as part of a series of steps or part of amore general structure, each said step may also be considered anindependent embodiment in itself, combinable with others.

The transitional terms “comprising,” “consisting essentially of,” and“consisting” are intended to connote their generally in acceptedmeanings in the patent vernacular; that is, (i) “comprising,” which issynonymous with “including,” “containing,” or “characterized by,” isinclusive or open-ended and does not exclude additional, unrecitedelements or method steps; (ii) “consisting of” excludes any element,step, or ingredient not specified in the claim; and (iii) “consistingessentially of” limits the scope of a claim to the specified materialsor steps and those that do not materially affect the basic and novelcharacteristic(s) of the claimed invention. Embodiments described interms of the phrase “comprising” (or its equivalents), also provide, asembodiments, those which are independently described in terms of“consisting of” and “consisting essentially of.” For those embodimentsprovided in terms of “consisting essentially of,” the basic and novelcharacteristic(s) is the facile operability of the methods to providesilylated products at meaningful yields (or the ability of the systemsused in such methods to provide the product compositions at meaningfulyields or the compositions derived therefrom) using only those activeingredients listed. In those embodiments that provide a compositionconsisting essentially of hydrosilane or organodisilane and strong base,the term refers to the fact that this composition is present in theabsence of silylatable aromatic, olefinic, or acetylenic substrates.

The term “meaningful product yields” is intended to reflect productyields of greater than 20%, but when specified, this term may also referto yields of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% or more,relative to the amount of original substrate.

When a list is presented, unless stated otherwise, it is to beunderstood that each individual element of that list, and everycombination of that list, is a separate embodiment. For example, a listof embodiments presented as “A, B, or C” is to be interpreted asincluding the embodiments, “A,” “B,” “C,” “A or B,” “A or C,” “B or C,”or “A, B, or C.” Similarly, a designation such as C₁₋₃ includes not onlyC₁₋₃, but also C₁, C₂, C₃, C₁₋₂, C₂₋₃, and C_(1,3), as separateembodiments.

Throughout this specification, words are to be afforded their normalmeaning, as would be understood by those skilled in the relevant art.However, so as to avoid misunderstanding, the meanings of certain termswill be specifically defined or clarified.

The term “alkyl” as used herein refers to a linear, branched, or cyclicsaturated hydrocarbon group typically although not necessarilycontaining 1 to about 24 carbon atoms, preferably 1 to about 12 carbonatoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl,isobutyl, tert-butyl, octyl, decyl, and the like, as well as cycloalkylgroups such as cyclopentyl, cyclohexyl and the like. Generally, althoughagain not necessarily, alkyl groups herein contain 1 to about 12 carbonatoms. The term also includes “lower alkyl” as separate embodiments,which refers to an alkyl group of 1 to 6 carbon atoms, and the specificterm “cycloalkyl” intends a cyclic alkyl group, typically having 4 to 8,preferably 5 to 7, carbon atoms. The term “substituted alkyl” refers toalkyl groups substituted with one or more substituent groups, and theterms “heteroatom-containing alkyl” and “heteroalkyl” refer to alkylgroups in which at least one carbon atom is replaced with a heteroatom.If not otherwise indicated, the terms “alkyl” and “lower alkyl” includelinear, branched, cyclic, unsubstituted, substituted, and/orheteroatom-containing alkyl and lower alkyl groups, respectively.

The term “alkylene” as used herein refers to a difunctional linear,branched, or cyclic alkyl group, where “alkyl” is as defined above.

The term “alkenyl” as used herein refers to a linear, branched, orcyclic hydrocarbon group of 2 to about 24 carbon atoms containing atleast one double bond, such as ethenyl, n-propenyl, isopropenyl,n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl,eicosenyl, tetracosenyl, and the like. Preferred alkenyl groups hereincontain 2 to about 12 carbon atoms. The term also includes “loweralkenyl” as separate embodiments, which refers to an alkenyl group of 2to 6 carbon atoms, and the specific term “cycloalkenyl” intends a cyclicalkenyl group, preferably having 5 to 8 carbon atoms. The term“substituted alkenyl” refers to alkenyl groups substituted with one ormore substituent groups, and the terms “heteroatom-containing alkenyl”and “heteroalkenyl” refer to alkenyl groups in which at least one carbonatom is replaced with a heteroatom. If not otherwise indicated, theterms “alkenyl” and “lower alkenyl” include linear, branched, cyclic,unsubstituted, substituted, and/or heteroatom-containing alkenyl andlower alkenyl groups, respectively.

The term “alkenylene” as used herein refers to a difunctional linear,branched, or cyclic alkenyl group, where “alkenyl” is as defined above.

The term “alkynyl” as used herein refers to a linear or branchedhydrocarbon group of 2 to about 24 carbon atoms containing at least onetriple bond, such as ethynyl, n-propynyl, and the like. Preferredalkynyl groups herein contain 2 to about 12 carbon atoms. The term“lower alkynyl” intends an alkynyl group of 2 to 6 carbon atoms. Theterm also includes “lower alkynyl” as separate embodiments, which refersto an alkynyl group substituted with one or more substituent groups, andthe terms “heteroatom-containing alkynyl” and “heteroalkynyl” refer toalkynyl in which at least one carbon atom is replaced with a heteroatom.If not otherwise indicated, the terms “alkynyl” and “lower alkynyl”include a linear, branched, unsubstituted, substituted, and/orheteroatom-containing alkynyl and lower alkynyl group, respectively.

The term “alkoxy” as used herein intends an alkyl group bound through asingle, terminal ether linkage; that is, an “alkoxy” group may berepresented as —O-alkyl where alkyl is as defined above. The term alsoincludes “lower alkoxy” as separate embodiments, which refers to analkoxy group containing 1 to 6 carbon atoms. Analogously, “alkenyloxy”and “lower alkenyloxy” respectively refer to an alkenyl and loweralkenyl group bound through a single, terminal ether linkage, and“alkynyloxy” and “lower alkynyloxy” respectively refer to an alkynyl andlower alkynyl group bound through a single, terminal ether linkage.

The term “aromatic” refers to the ring moieties which satisfy the Hückel4n+2 rule for aromaticity, and includes both aryl (i.e., carbocyclic)and heteroaryl (also called heteroaromatic) structures, including aryl,aralkyl, alkaryl, heteroaryl, heteroaralkyl, or alk-heteroaryl moieties,or pre-polymeric (e.g., monomeric, dimeric), oligomeric or polymericanalogs thereof.

The term “aryl” as used herein, and unless otherwise specified, refersto a carbocyclic aromatic substituent or structure containing a singlearomatic ring or multiple aromatic rings that are fused together,directly linked, or indirectly linked (such that the different aromaticrings are bound to a common group such as a methylene or ethylenemoiety). Preferred aryl groups contain 6 to 24 carbon atoms, andparticularly preferred aryl groups contain 6 to 14 carbon atoms.Exemplary aryl groups contain one aromatic ring or two fused or linkedaromatic rings, e.g., phenyl, naphthyl, biphenyl, diphenylether,diphenylamine, benzophenone, and the like. “Substituted aryl” refers toan aryl moiety substituted with one or more substituent groups, and theterms “heteroatom-containing aryl” and “heteroaryl” refer to arylsubstituents in which at least one carbon atom is replaced with aheteroatom, as will be described in further detail infra.

Unless otherwise specified, as used herein in the context of silylationreactions, the term “C—H bond” refers to an acetylenic or alkynyl C—Hbond, a terminal olefinic C—H bond, an aromatic (aryl or heteroaryl)C—Hbond, or C—H bond of an alkyl, alkoxy, or alkylene group positionedalpha to an aromatic/heteroaromatic ring system (e.g., benzylic, or 2,5-dimethylthiophene substrates), such as previously described in any ofthe references cited herein showing the propensity to be silylated usingsimultaneous mixing of the precursor substrate,hydrosilane/organosilane, and strong bases, including hydroxides.

The term “aryloxy” as used herein refers to an aryl group bound througha single, terminal ether linkage, wherein “aryl” is as defined above. An“aryloxy” group may be represented as —O-aryl where aryl is as definedabove. Preferred aryloxy groups contain 6 to 24 carbon atoms, andparticularly preferred aryloxy groups contain 6 to 14 carbon atoms.Examples of aryloxy groups include, without limitation, phenoxy,o-halo-phenoxy, m-halo-phenoxy, p-halo-phenoxy, o-methoxy-phenoxy,m-methoxy-phenoxy, p-methoxy-phenoxy, 2,4-dimethoxy-phenoxy,3,4,5-trimethoxy-phenoxy, and the like.

The term “alkaryl” refers to an aryl group with an alkyl substituent,and the term “aralkyl” refers to an alkyl group with an arylsubstituent, wherein “aryl” and “alkyl” are as defined above. Preferredalkaryl and aralkyl groups contain 7 to 24 carbon atoms, andparticularly preferred alkaryl and aralkyl groups contain 7 to 16 carbonatoms. Alkaryl groups include, for example, p-methylphenyl,2,4-dimethylphenyl, p-cyclohexylphenyl, 2, 7-dimethylnaphthyl,7-cyclooctylnaphthyl, 3-ethyl-cyclopenta-1,4-diene, and the like.Examples of aralkyl groups include, without limitation, benzyl,2-phenyl-ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 5-phenyl-pentyl,4-phenylcyclohexyl, 4-benzylcyclohexyl, 4-phenylcyclohexylmethyl,4-benzylcyclohexylmethyl, and the like. The terms “alkaryloxy” and“aralkyloxy” refer to substituents of the formula —OR wherein R isalkaryl or aralkyl, respectively, as just defined.

The term “acyl” refers to substituents having the formula —(CO)-alkyl,—(CO)-aryl, or —(CO)-aralkyl, and the term “acyloxy” refers tosubstituents having the formula —O(CO)-alkyl, —O(CO)-aryl, or—O(CO)-aralkyl, wherein “alkyl,” “aryl, and “aralkyl” are as definedabove.

The terms “cyclic” and “ring” refer to alicyclic or aromatic groups thatmay or may not be substituted and/or heteroatom-containing, and that maybe monocyclic, bicyclic, or polycyclic. The term “alicyclic” is used inthe conventional sense to refer to an aliphatic cyclic moiety, asopposed to an aromatic cyclic moiety, and may be monocyclic, bicyclic,or polycyclic. The term “acyclic” refers to a structure in which thedouble bond is not contained within a ring structure.

The terms “halo,” “halide,” and “halogen” are used in the conventionalsense to refer to a chloro, bromo, fluoro, or iodo substituent.

“Hydrocarbyl” refers to univalent hydrocarbyl radicals containing 1 toabout 30 carbon atoms, preferably 1 to about 24 carbon atoms, mostpreferably 1 to about 12 carbon atoms, including linear, branched,cyclic, saturated, and unsaturated species, such as alkyl groups,alkenyl groups, aryl groups, and the like. The term “lower hydrocarbyl”intends a hydrocarbyl group of 1 to 6 carbon atoms, preferably 1 to 4carbon atoms, and the term “hydrocarbylene” intends a divalenthydrocarbyl moiety containing 1 to about 30 carbon atoms, preferably 1to about 24 carbon atoms, most preferably 1 to about 12 carbon atoms,including linear, branched, cyclic, saturated and unsaturated species.The term “lower hydrocarbylene” intends a hydrocarbylene group of 1 to 6carbon atoms. “Substituted hydrocarbyl” refers to hydrocarbylsubstituted with one or more substituent groups, and the terms“heteroatom-containing hydrocarbyl” and “heterohydrocarbyl” refer tohydrocarbyl in which at least one carbon atom is replaced with aheteroatom. Similarly, “substituted hydrocarbylene” refers tohydrocarbylene substituted with one or more substituent groups, and theterms “heteroatom-containing hydrocarbylene” and heterohydrocarbylene”refer to hydrocarbylene in which at least one carbon atom is replacedwith a heteroatom. Unless otherwise indicated, the term “hydrocarbyl”and “hydrocarbylene” are to be interpreted as including substitutedand/or heteroatom-containing hydrocarbyl and hydrocarbylene moieties,respectively.

The term “heteroatom-containing” as in a “heteroatom-containinghydrocarbyl group” refers to a hydrocarbon molecule or a hydrocarbylmolecular fragment in which one or more carbon atoms is replaced with anatom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus orsilicon, typically nitrogen, oxygen or sulfur. Similarly, the term“heteroalkyl” refers to an alkyl substituent that isheteroatom-containing, the term “heterocyclic” refers to a cyclicsubstituent that is heteroatom-containing, the terms “heteroaryl” andheteroaromatic” respectively refer to “aryl” and “aromatic” substituentsthat are heteroatom-containing, and the like. It should be noted that a“heterocyclic” group or compound may or may not be aromatic, and furtherthat “heterocycles” may be monocyclic, bicyclic, or polycyclic asdescribed above with respect to the term “aryl.” Examples of heteroalkylgroups include alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylatedamino alkyl, and the like. Non-limiting examples of heteroarylsubstituents include pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl,indolyl, pyrimidinyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, etc., andexamples of heteroatom-containing alicyclic groups are pyrrolidino,morpholino, piperazino, piperidino, etc.

As used herein, the terms “substrate” or “organic substrate” areintended to connote both discrete small molecules (sometimes describedas “organic compounds”) and oligomers and polymers containing a C—Hgroup capable of silylation under the described reaction conditions. Theterm “aromatic moieties” is intended to refer to those portions of thecompounds, pre-polymers (i.e., monomeric compounds capable ofpolymerizing), oligomers, or polymers having at least one of theindicated aromatic structures. Where shown as structures, the moietiescontain at least that which is shown, as well as containing furtherfunctionalization, substituents, or both, including but not limited tothe functionalization described as “Fn” herein.

By “substituted” as in “substituted hydrocarbyl,” “substituted alkyl,”“substituted aryl,” and the like, as alluded to in some of theaforementioned definitions, is meant that in the hydrocarbyl, alkyl,aryl, heteroaryl, or other moiety, at least one hydrogen atom bound to acarbon (or other) atom is replaced with one or more non-hydrogensubstituents. Examples of such substituents include, without limitation:functional groups referred to herein as “Fn,” such as halo (e.g., F, Cl,Br, I), hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₂-C₂₄ alkenyloxy, C₂-C₂₄alkynyloxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl(including C₁-C₂₄ alkylcarbonyl (—CO-alkyl) and C₆-C₂₄ arylcarbonyl(—CO-aryl)), acyloxy (—O-acyl, including C₂-C₂₄ alkylcarbonyloxy (—O—CO—alkyl) and C₆-C₂₄ arylcarbonyloxy (—O—CO-aryl)), C₂-C₂₄ alkoxycarbonyl((CO)—O-alkyl), C₆-C₂₄ aryloxycarbonyl (—(CO)—O-aryl), halocarbonyl(—CO)—X where X is halo), C₂-C₂₄ alkylcarbonato (—O—(C₀)—O-alkyl),C₆-C₂₄ arylcarbonato (—O—(CO)—O-aryl), carboxy (—COOH), carboxylato(—COO—), carbamoyl (—(CO)—NH₂), mono-(C₁-C₂₄ alkyl)-substitutedcarbamoyl (—(CO)NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substitutedcarbamoyl (—(CO)—N(C₁-C₂₄ alkyl)₂), mono-(C₁-C₂₄ haloalkyl)-substitutedcarbamoyl (—(CO)—NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ haloalkyl)-substitutedcarbamoyl (—(CO)—N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substitutedcarbamoyl (—(CO)—NH-aryl), di-(C₅-C₂₄ aryl)substituted carbamoyl(—(CO)—N(C₅-C₂₄ aryl)₂), di-N—(C₁-C₂₄ alkyl), N—(C₅-C₂₄aryl)-substituted carbamoyl, thiocarbamoyl (—(CS)—NH₂), mono-(C₁-C₂₄alkyl)-substituted thiocarbamoyl (—(CO)—NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄alkyl)-substituted thiocarbamoyl (—(CO)—N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄aryl)substituted thiocarbamoyl (—(CO)—NH-aryl), di-(C₅-C₂₄aryl)-substituted thiocarbamoyl (—(CO)—N(C₅-C₂₄ aryl)₂), di-N—(C₁-C₂₄alkyl), N—(C₅-C₂₄ aryl)-substituted thiocarbamoyl, carbamido(—NH—(CO)—NH₂), cyano (—C≡N), cyanato (—O—C═N), thiocyanato (—S—C═N),formyl (—(CO)—H), thioformyl (—(CS)—H), amino (—NH₂), mono-(C₁-C₂₄alkyl)-substituted amino, di-(C₁-C₂₄ alkyl)-substituted amino,mono-(C₅-C₂₄ aryl)substituted amino, di-(C₅-C₂₄ aryl)-substituted amino,C₁-C₂₄ alkylamido (—NH—(CO)-alkyl), C₆-C₂₄ arylamido (—NH—(CO)-aryl),imino (—CR═NH where R=hydrogen, C₁-C₂₄ alkyl, C5-C24 aryl, C₆-C₂₄alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (—CR═N(alkyl), whereR=hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl,etc.), arylimino (—CR═N(aryl), where R=hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), nitro (—NO₂), nitroso(—NO), sulfo (—SO₂OH), sulfonate (SO₂O—), C₁-C₂₄ alkylsulfanyl(—S-alkyl; also termed “alkylthio”), C₅-C₂₄ arylsulfanyl (—S-aryl; alsotermed “arylthio”), C₁-C₂₄ alkylsulfinyl (—(SO)-alkyl), C₅-C₂₄arylsulfinyl (—(SO)-aryl), C₁-C₂₄ alkylsulfonyl (—SO₂-alkyl), C₁-C₂₄monoalkylaminosulfonyl-SO₂—N(H) alkyl), C₁-C₂₄dialkylaminosulfonyl-SO₂—N(alkyl)₂, C₅-C₂₄ arylsulfonyl (—SO₂-aryl),boryl (—BH₂), borono (—B(OH)₂), boronato (—B(OR)₂ where R is alkyl orother hydrocarbyl), phosphono (—P(O)(OH)₂), phosphonato (—P(O)(O)₂),phosphinato (P(O)(O—)), phospho (—PO₂), and phosphine (—PH2); and thehydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂, alkyl, morepreferably C₁-C₆ alkyl), C₂-C₂₄ alkenyl (preferably C₂-C₁₂ alkenyl, morepreferably C₂-C₆ alkenyl), C₂-C₂₄ alkynyl (preferably C₂-C₁₂ alkynyl,more preferably C₂-C₆ alkynyl), C₅-C₂₄ aryl (preferably C₅-C₂₄ aryl),C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl(preferably C₆-C₁₆ aralkyl). Within these substituent structures, the“alkyl,” “alkylene,” “alkenyl,” “alkenylene,” “alkynyl,” “alkynylene,”“alkoxy,” “aromatic,” “aryl,” “aryloxy,” “alkaryl,” and “aralkyl”moieties may be optionally fluorinated or perfluorinated. Additionally,reference to alcohols, aldehydes, amines, carboxylic acids, ketones, orother similarly reactive functional groups also includes their protectedanalogs. For example, reference to hydroxy or alcohol also includesthose substituents wherein the hydroxy is protected by acetyl (Ac),benzoyl (Bz), benzyl (Bn), β-Methoxyethoxymethyl ether (MEM),dimethoxytrityl, [bis-(4-methoxyphenyl)phenylmethyl] (DMT),methoxymethyl ether (MOM), methoxytrityl[(4-methoxyphenyl)diphenylmethyl, MMT), p-methoxybenzyl ether (PMB),methylthiomethyl ether, pivaloyl (Piv), tetrahydropyranyl (THP),tetrahydrofuran (THF), trityl (triphenylmethyl, Tr), silyl ether (mostpopular ones include trimethylsilyl (TMS), tert-butyldimethylsilyl(TBDMS), tri-iso-propylsilyloxymethyl (TOM), and triisopropylsilyl(TIPS) ethers), ethoxyethyl ethers (EE). Reference to amines alsoincludes those substituents wherein the amine is protected by a BOCglycine, carbobenzyloxy (Cbz), p-methoxybenzyl carbonyl (Moz or MeOZ),tert-butyloxycarbonyl (BOC), 9-fluorenylmethyloxycarbonyl (FMOC), acetyl(Ac), benzoyl (Bz), benzyl (Bn), carbamate, p-methoxybenzyl (PMB),3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts) group, orsulfonamide (Nosyl & Nps) group. Reference to substituent containing acarbonyl group also includes those substituents wherein the carbonyl isprotected by an acetal or ketal, acylal, or diathane group. Reference tosubstituent containing a carboxylic acid or carboxylate group alsoincludes those substituents wherein the carboxylic acid or carboxylategroup is protected by its methyl ester, benzyl ester, tert-butyl ester,an ester of 2,6-disubstituted phenol (e.g. 2,6-dimethylphenol,2,6-diisopropylphenol, 2,6-di-tert-butylphenol), a silyl ester, anorthoester, or an oxazoline. Preferred substituents are those identifiedherein as not or less affecting the silylation chemistries, for example,including those substituents comprising alkyls; alkoxides, aryloxides,aralkylalkoxides, protected carbonyl groups; aryls optionallysubstituted with F, Cl, —CF₃; epoxides; N-alkyl aziridines; cis- andtrans-olefins; acetylenes; pyridines, primary, secondary and tertiaryamines; phosphines; and hydroxides.

By “functionalized” as in “functionalized hydrocarbyl,” “functionalizedalkyl,” “functionalized olefin,” “functionalized cyclic olefin,” and thelike, is meant that in the hydrocarbyl, alkyl, aryl, heteroaryl, olefin,cyclic olefin, or other moiety, at least one hydrogen atom bound to acarbon (or other) atom is replaced with one or more functional groupssuch as those described herein and above. The term “functional group” ismeant to include any of the substituents described herein with the ambitof “Fn.”.

In addition, the aforementioned functional groups may, if a particulargroup permits, be further substituted with one or more additionalfunctional groups or with one or more hydrocarbyl moieties such as thosespecifically enumerated above. Analogously, the above-mentionedhydrocarbyl moieties may be further substituted with one or morefunctional groups or additional hydrocarbyl moieties such as thosespecifically enumerated.

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, the phrase “optionally substituted” means that anon-hydrogen substituent may or may not be present on a given atom ororganic moiety, and, thus, the description includes structures wherein anon-hydrogen substituent is present and structures wherein anon-hydrogen substituent is not present.

As used herein, the terms “organosilane” or “hydrosilane” may be usedinterchangeably and refer to a compound or reagent having at least onesilicon-hydrogen (Si—H) bond and preferably at least onecarbon-containing moiety. The hydrosilane may further contain asilicon-carbon, a silicon-oxygen (i.e., encompassing the term“organosiloxane”), a silicon-nitrogen bond, or a combination thereof,and may be monomeric, or contained within an oligomeric or polymericframework, including being tethered to a heterogeneous or homogeneoussupport structure. The term “hydrosilane” also include deuterosilanes,in which the corresponding S—H bond is enriched in Si-D cogeners.

As used herein, the terms “organodisilane” and “disilane” are usedinterchangeably and refer to a compound or reagent having at least oneSi—Si bond. These terms include those embodiments where the disilanecontains at least one Si—H bond and those embodiments wherein thedisilane no silicon-hydrogen (Si—H) bonds. While the present disclosurerefers to the reaction of compounds having Si—Si bonds, the optionalpresence of Si—H bonds may allow the reaction to proceed throughreaction manifolds also described for silylations using organosilanereagents. Such a Si—H pathway is not required for silylation to proceedin the disilane systems, but where the silylating reagent contains botha Si—Si and Si—H bond, the reactions may operate in parallel with oneanother. The organodisilane may further contain a silicon-carbon, asilicon-oxygen, a silicon-nitrogen bond, or a combination thereof, andmay be monomeric, or contained within an oligomeric or polymericframework, including being tethered to a heterogeneous or homogeneoussupport structure.

As used herein, unless explicitly stated to the contrary, theorganosilanes or organodisilanes are intended to refer to materials thatcontain no Si-halogen bonds. However, in some embodiments, theorganosilanes or organodisilanes may contain a Si-halogen bond.

As used herein, the terms “silylating” or “silylation” refer to theforming of carbon-silicon bonds, in a position previously occupied by acarbon-hydrogen bond. Silylating may be seen as dehydrogenative couplingof a C—H and Si—H bond or a C—H and Si—Si bond to form a C—Si bond.

As used herein, the term “substantially free of a transition-metalcompound” is intended to reflect that the system is stable (in thecontext of the preconditioned compositions) and effective for itsintended purpose of silylating the C—H bonds under the relatively mildconditions described herein(in the case of the methods), even in theabsence of any exogenous (i.e., deliberately added or otherwise)transition-metal catalyst(s). While certain embodiments provide thattransition metals, including those capable of catalyzing silylationreactions, may be present within the systems or methods described hereinat levels normally associated with such catalytic activity (for example,in the case where the substrates comprise metallocenes), the presence ofsuch metals (either as catalysts or spectator compounds) is not requiredand in many cases is not desirable. As such, in many preferredembodiments, the system and methods are “substantially free oftransition-metal compounds.” Unless otherwise stated, then, the term“substantially free of a transition-metal compound” is defined toreflect that the total level of transition metal within the silylatingsystem, independently or in the presence of organic substrate, is lessthan about 5 ppm, as measured by ICP-MS. When expressly stated as such,additional embodiments also provide that the concentration of transitionmetals is less than about 10 wt %, 5 wt %, 1 wt %, 100 ppm, 50 ppm, 30ppm, 25 ppm, 20 ppm, 15 ppm, 10 ppm, or 5 ppm to about 1 ppm or 0 ppm.As used herein, the term “transition metal” is defined to included-block elements, for example Ag, Au, Co, Cr, Rh, Ir, Fe, Ru, Os, Ni,Pd, Pt, Cu, Zn, or combinations thereof. In further specific independentembodiments, the concentration of Ni, as measured by ICP-MS, is lessthan 25 ppm, less than 10 ppm, less than 5 ppm, or less than 1 ppm.

Likewise, the term “substantial absence of a heteroaromatic, olefinic,or acetylenic substrate capable of C—H silylation” is intended toreflect that the compounds or preconditioned compositions containsubstoichiometric amounts of these materials relative to the amount ofprecursor hydrosilane, or the absence of added substrate materials, andpreferably no added substrates capable of being otherwise silylated at aC—H position, under the stated conditions. Such unsaturated organicsubstrate especially refer to the heteraromatic substrate, but also theterminal olefinic or acetylylinic substrates described in the patentapplications cited elsewhere herein.

While it may not be necessary to limit the system's exposure to waterand oxygen, the presence of these materials may materially affect thestability of the preconditioned mixtures, the hydride compounds, or therate of the subsequent silylation reactions, for example by theformation of free radical intermediates. In some embodiments, thechemical systems and the methods are substantially free of water,oxygen, or both water and oxygen. In other embodiments, air and/or waterare present. Unless otherwise specified, the term “substantially free ofwater” refers to levels of water less than about 500 ppm and“substantially free of oxygen” refers to oxygen levels corresponding topartial pressures less than 1 torr. Where stated, additional independentembodiments may provide that “substantially free of water” refers tolevels of water less than 1.5 wt %, 1 wt %, 0.5 wt %, 1000 ppm, 500 ppm,250 ppm, 100 ppm, 50 ppm, 10 ppm, or 1 ppm and “substantially free ofoxygen” refers to oxygen levels corresponding to partial pressures lessthan 50 torr, 10 torr, 5 torr, 1 torr, 500 millitorr, 250 millitorr, 100millitorr, 50 millitorr, or 10 millitorr. In the General Proceduredescribed herein, deliberate efforts were made to exclude both water andoxygen, unless otherwise specified.

The term “terminally silylated olefinic product” refers to an olefinicproduct of the reactions as described herein, and includes terminallysubstituted vinyl silanes or allylic silanes. The term “terminallysilylated olefinic moiety” refers to the silyl moiety of the terminallysilylated olefinic product, whether the product is an allylic or vinylsilyl compound. The term “terminally hydrosilylated product” refers to aproduct in wherein the silyl group is positioned at a terminal positionof an ethylene linkage, typically the result of an anti-Markovnikovhydrosilylation addition to a vinyl aromatic substrate.

The following listing of Embodiments is intended to complement, ratherthan displace or supersede, the previous descriptions.

Embodiment 1. A composition prepared by preconditioning a mixture of:

-   -   (a) a precursor hydrosilane or organodisilane; and    -   (b) a base comprising or consisting essentially of potassium        hydroxide, a potassium alkoxide, a potassium silanolate (e.g.,        KOTMS), rubidium hydroxide, a rubidium alkoxide, a rubidium        silanolate, cesium hydroxide, a cesium alkoxide, a cesium        silanolate, a potassium amide (e.g., potassium        bis(trimethylsilyl) amide), a potassium graphite (e.g., KC₈), or        a combination thereof;

the preconditioning comprising or consisting essentially of holding themixture of combined hydrosilane and the base at conditions sufficient toproduce the composition capable of initiating measurable silylation of1-methyl indole at a temperature of 45° C. (or less) with an inductionperiod of less than 30, 25, 20, 15, 10, 5, or 1 minutes. In certainAspects of this Embodiment, the composition is free of addedheteroaromatic, olefinic, or acetylenic substrates.

Embodiment 2. A composition comprising a Si—H-based species derived orderivable from the preconditioning reaction as described in Embodiment 1between:

-   -   (a) a precursor hydrosilane; and    -   (b) a base comprising or consisting essentially of potassium        hydroxide, a potassium alkoxide, a potassium silanolate (e.g.,        KOTMS), rubidium hydroxide, a rubidium alkoxide, a rubidium        silanolate, cesium hydroxide, a cesium alkoxide, a cesium        silanolate, a potassium amide (e.g., potassium        bis(trimethylsilyl) amide), or a combination thereof; and

wherein the precursor hydrosilane exhibits an absorption peak in theSi—H stretching region of infrared spectrum and the Si—H-based speciesexhibits an absorption peak in the Si—H stretching region of an infraredspectrum that is of lower energy than the absorption peak of theprecursor hydrosilane, when evaluated under comparable conditions. Insome Aspects of this Embodiment, the Si—H-based species is or comprisesan hypercoordinated silicon species containing a Si—H bond. In certainAspects of this Embodiment, the composition is free of addedheteroaromatic, olefinic, or acetylenic substrates. The term “derivable”connotes that the composition may be derived, but is not necessarilyderived, from the reaction between the precursor hydrosilane and thebase.

Embodiment 3. The composition of Embodiment 1 or 2, wherein thecomposition further comprises a solvent. In other Aspects of thisEmbodiment, the composition is solvent-free (i.e., the hydrosilane ororganodisilane and the base are present as a neat mixture). In someAspects of this Embodiment, the composition is a solution comprising ahydrocarbon solvent. In some preferred Aspects of this Embodiment, thecomposition is a solution comprising an oxygen donor-containing solvent,such as described elsewhere herein, preferably an ether-type solvent,more preferably an optionally substituted tetrahydrofuran, for example2-methyl tetrahydrofuran.

Embodiment 4. The composition of any one of Embodiment 1 to 3, whereinthe base comprises potassium hydroxide, rubidium hydroxide, or cesiumhydroxide.

Embodiment 5. The composition of any one of Embodiments 1 to 3, whereinthe base comprises potassium hydroxide.

Embodiment 6. The composition of any one of Embodiment 1 to 3, whereinthe base comprises a potassium alkoxide, a rubidium alkoxide, or acesium alkoxide.

Embodiment 7. The composition of any one of Embodiments 1 to 3, whereinthe base comprises a potassium alkoxide.

Embodiment 8. The composition of any one of Embodiments 1, 6, or 7,wherein the alkoxide comprises a C₁₋₆ alkoxide, such as methoxide,ethoxide, propoxide, or butoxide, preferably tert-butyl butoxide.

Embodiment 9. The composition of any one of Embodiments 1 to 8, whereinthe precursor hydrosilane is of the Formula (I) or Formula (II):

(R)_(3−m)Si(H)_(m+1)  (I)

(R)_(3−m)(H)_(m)Si—Si(R)_(2−m)(H)_(m+1)  (II)

where: m is independently 0, 1, or 2; and each R is independentlyoptionally substituted C₁₋₂₄ alkyl or heteroalkyl, optionallysubstituted C₂₋₂₄ alkenyl, optionally substituted C₂₋₂₄ alkynyl,optionally substituted C₆₋₁₂ aryl, C₃₋₁₂ heteroaryl, optionallysubstituted C₇₋₁₃ alkaryl, optionally substituted C₄₋₁₂ heteroalkaryl,optionally substituted C₇₋₁₃ aralkyl, optionally substituted C₄₋₁₂heteroaralkyl, optionally substituted —O—C₁₋₂₄ alkyl, optionallysubstituted C₆₋₁₂ aryloxy, optionally substituted C₃₋₁₂ heteroaryloxy,optionally substituted C₇₋₁₃ alkaryloxy, optionally substituted C₄₋₁₂heteroalkaryloxy, optionally substituted C₆₋₁₂ aralkoxy, or C₄₋₁₂heteroaralkoxy, and, if substituted, the substituents may bephosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C₁-C₂₀ alkylsulfinyl, 5 to 12 ring-membered arylsulfinyl,sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl,carboxyl, carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano,cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy,styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, orhalogen, or a metal-containing or metalloid-containing group, where themetalloid is Sn or Ge, where the substituents may optionally provide atether to an insoluble or sparingly soluble support media comprisingalumina, silica, or carbon. In certain Aspects of this Embodiment, theprecursor organodisilane is of the Formula (III)

(R′)₃Si—Si(R′)₃  (III)

where R′ is R, as defined above, or may additionally comprise optionallysubstituted alkoxy or aryloxy moieties or trimethylsiloxy. In otherAspects of this Embodiment, R or R′ is independently an optionallysubstituted alkyl, alkenyl, alkynyl, aryl, and/or heteroaryl moiety, thespecifics of which are further described elsewhere. R′ may alsoindependently comprise optionally substituted alkoxy or aryloxy moietiesor trimethylsiloxy.

Embodiment 10. The composition of any one of Embodiments 1 to 9, whereinthe at least one hydrosilane is (R)₃SiH or (R)₂SiH₂, where R isindependently at each occurrence C₁₋₆ alkyl, phenyl, tolyl, orpyridinyl. In certain Aspects of this Embodiment, R is independently ateach occurrence methyl, ethyl, propyl, butyl, propyl, phenyl, biphenyl,benzyl, or pyridinyl, for example EtMe₂SiH, PhMe₂SiH, BnMe₂SiH,(n-Bu)₃SiH, Et₂SiH₂, Me₃SiH, Et₃SiH, n-Pr₃SiH, i-Pr₃SiH, n-Bu₃SiH,sec-Bu₃SiH, tert-Bu₃SiH, Me₂(pyridinyl)SiH, or Me₃Si—SiMe₂H. In certainAspects of this Embodiment, these substituents are optionallysubstituted.

Embodiment 11. The composition of Embodiment 10, that is a solution,wherein the base comprises potassium tert-butoxide.

Embodiment 12. The composition of any one of Embodiments 1 to 11,wherein the composition contains no added transition metal or transitionmetal species. In certain Aspects of this Embodiment, transition metalsor transition metal species are present at less than 1%, 1000 ppm, 100ppm, 50 ppm, or 10 ppm, based on the total weight of the composition.

Embodiment 13. The composition of any one of Embodiments 1 to 11,wherein the composition is an ether-based solution, most preferablytetrahydrofuran or 2-methyl-tetrahydrofuran.

Embodiment 14. The composition of Embodiment 13, which intetrahydrofuran further exhibits an electron paramagnetic resonance(EPR) signal in THF centered at g=2.0007 substantially as shown in FIG.3.

Embodiment 15. A compound, or a composition comprising the compounditself, having an optionally solvated silicon hydride structure ofFormula (IV):

or a geometric isomer thereof, wherein

-   -   M⁺ is or comprises a cation comprising potassium, rubidium,        cesium, or a combination thereof;    -   —OR^(B) is or comprises hydroxide, an alkoxide, an alkyl        silanolate; or a combination thereof; and    -   —R^(S) is or comprises H, —R, or —Si(R)_(3−m)H_(m), or a        combination thereof    -   where m is and R is as described elsewhere herein; or an isomer        thereof.

Embodiment 16. A compound that is the addition product of (a) potassiumhydroxide, a potassium alkoxide, a potassium silanolate, rubidiumhydroxide, a rubidium alkoxide, a rubidium silanolate, cesium hydroxide,a cesium alkoxide, a cesium silanolate, or a combination thereof with(b) a precursor hydrosilane of Formula (I) or (II), or any of theindividual precursor hydrosilanes as described elsewhere herein.

Embodiment 17. A compound or composition of any one of Embodiments 1 to16 that is free of added heteroaromatic, olefinic, or acetylenicsubstrates. In certain Aspects of this Embodiment, the term “free”connotes free of added substrates.

Embodiment 18. A method comprising silylating an organic substratehaving a C—H bond or an alcoholic O—H bond, the method comprisingcontacting the organic substrate with a composition or compound of anyone of Embodiments 1 to 17;

wherein the contacting results in the formation of a C—Si bond in theposition previously occupied by the C—H bond, or the formation of anO—Si bond in the position previously occupied by the O—H bond;

wherein the C—H bond is:

(a) located on a heteroaromatic moiety;

(b) located on an alkyl, alkoxy, or alkylene moiety positioned alpha toan aryl or heteroaryl moiety;

(c) an alkynyl C—H bond; or

(d) a terminal olefinic C—H bond; and wherein the preconditioned mixtureis able to initiate measurable silylation of 1-methyl indole at atemperature of 45° C. (or less) with an induction period of less than30, 25, 20, 15, 10, 5, or 1 minutes. Each of the substrates or classessubstrates is considered an independent Embodiment. In certainindividual Aspects of this Embodiment, the precursor hydrosilane is acompound of Formula (I) or (II), or any individual hydrosilane asdescribed herein.

Embodiment 19. A method comprising silylating at least one organicsubstrate containing a C—H bond or —OH bond, the method comprisingcontacting the organic substrate with

-   -   (a) a precursor hydrosilane; and    -   (b) a base comprising or consisting essentially of cesium        hydroxide, rubidium hydroxide, KC₈, or a combination thereof;    -   wherein the C—H bond is:    -   (a) located on a heteroaromatic moiety;    -   (b) located on an alkyl, alkoxy, or alkylene moiety positioned        alpha to an aryl or heteroaryl moiety;    -   (c) an alkynyl C—H bond; or    -   (d) a terminal olefinic C—H bond; and

wherein the contacting results in the formation of a C—Si bond in theposition previously occupied by the C—H bond or an O—Si bond in theposition previously occupied by the O—H bond. Each of the substrates orclasses of these substrates is considered an independent Embodiment. Incertain individual Aspects of this Embodiment, the precursor hydrosilaneis a compound of Formula (I) or (II), or any individual hydrosilane asdescribed herein. In other individual Aspects of this Embodiment, theprecursor organodisilane is a compound of Formula (III), or anyindividual hydrosilane as described herein

Embodiment 20. The method of Embodiment 19, wherein the precursorhydrosilane or organodisilane and the base are preconditioned beforecontacting with the organic substrate, the preconditioning comprisingholding a mixture comprising the precursor hydrosilane and the base atone or more temperatures in a range of from about 25° C. to about 125°C. for a time in a range of from about 30 minutes to about 24 hours, thecombination of time and temperature being sufficient to produce thecomposition capable of initiating measurable silylation of 1-methylindole at a temperature of 45° C. (or less) with an induction period ofless than 30, 25, 20, 15, 10, 5, or 1 minutes.

Embodiment 21. The method of any one of Embodiments 18 to 20, whereinthe organic substrate is a heteroaromatic moiety, for example comprisingan optionally substituted furan, pyrrole, thiophene, pyrazole,imidazole, triazole, isoxazole, oxazole, thiazole, isothiazole,oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazone,benzofuran, benzothiophene, isobenzofuran, isobenzothiophene, indole,isoindole, indolizine, indazole, azaindole, benzisoxazole, benzoxazole,quinoline, isoquinoline, cinnoline, quinazoline, naphthyridine,2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, ordibenzothiophene moiety. In certain Aspects of this Embodiment, theorganic substrate is a heteroaryl substrate as described in U.S. patentapplication Ser. No. 14/043,929, filed Oct. 2, 2013 (heteroaromaticswith alkoxides), now U.S. Pat. No. 9,000,167 or Ser. No. 14/818,417,filed Aug. 5, 2015 (heteroaromatics with hydroxides), each of which isincorporated by reference herein at least for these teachings.

Embodiment 22. The method of any one of Embodiments 18 to 20, whereinthe organic substrate comprises as alkynyl C—H bond having a formula:

R³—C≡C—H,

where R³ comprises an optionally substituted C₁₋₁₈ alkyl, optionallysubstituted C₂₋₁₈ alkenyl, optionally substituted C₂₋₁₈ alkynyl,optionally substituted C₆₋₁₈ aryl, optionally substituted C₆₋₁₈ aryloxy,optionally substituted C₇₋₁₈ aralkyl, optionally substituted C₇₋₁₈aralkyloxy, optionally substituted C₃₋₁₈ heteroaryl, optionallysubstituted C₃₋₁₈ heteroaryloxy, optionally substituted C₄₋₁₈heteroarylalkyl, optionally substituted C₄₋₁₈ heteroaralkyloxy, oroptionally substituted metallocene. In certain Aspects of thisEmbodiment, the organic substrate is an alkyne as described in U.S.patent application Ser. No. 14/841,964 filed Sep. 1, 2015 (alkynes), nowU.S. Pat. No. 9,556,206, which is incorporated by reference herein atleast for these teachings.

Embodiment 23. The method of any one of Embodiments 18 to 20, whereinthe at least one organic substrate comprises a terminal olefin has aFormula (V):

where p is 0 or 1; R¹ and R² independently comprises H, an optionallysubstituted C₁₋₁₈ alkyl, optionally substituted C₂₋₁₈ alkenyl,optionally substituted C₂₋₁₈ alkynyl, optionally substituted C₆₋₁₈ aryl,optionally substituted C₁₋₁₈ heteroalkyl, optionally substituted 5-6ring membered heteroaryl, optionally substituted 5-6 ring memberedaralkyl, optionally substituted 5-6 ring membered heteroaralkyl, oroptionally substituted metallocene, provided that R¹ and R² are not bothH. In certain Aspects of this Embodiment, the organic substrate is anyone having a terminal olefin as described in U.S. patent applicationSer. No. 15/166,405 (terminal olefins), filed May 27, 2016, which isincorporated by reference herein at least for these teachings.

Embodiment 23. The method of any one of Embodiments 18 to 20, whereinthe at least one organic substrate comprises an alcoholic —OH group,having a structure of Formula (VIA) or (VIB).

R⁴—OH  (VIA)

HO—R⁵—OH  (VIB),

where R⁴ comprises an optionally substituted C₁₋₂₄ alkyl, optionallysubstituted C₂₋₂₄ alkenyl, optionally substituted C₂₋₂₄ alkynyl,optionally substituted C₆₋₂₄ aryl, optionally substituted C₁₋₂₄heteroalkyl, optionally substituted 5- or 6-ring membered heteroaryl,optionally substituted C₇₋₂₄ aralkyl, optionally substitutedheteroaralkyl, or optionally substituted metallocene; and where R⁵comprises an optionally substituted C₂₋₁₂ alkylene, optionallysubstituted C₂₋₁₂ alkenylene, optionally substituted C₆₋₂₄ arylene,optionally substituted C₁₋₁₂ heteroalkylene, or an optionallysubstituted 5- or 6-ring membered heteroarylene. In some Aspect of thisEmbodiments, the organic substrate having at least one organic alcoholmoiety is or comprises an optionally substituted catechol moiety or hasa Formula (IV):

wherein n is from 0 to 6, preferably 0 or 1;

R^(M) and R^(N) are independently H or methyl

R^(D), R^(E), R^(F), and R^(G) are independently H, C₁₋₆ alkyl, C₁₋₆alkenyl, optionally substituted phenyl, optionally substituted benzyl,or an optionally substituted 5- or 6-ring membered heteroaryl, whereinthe optional substituents are C₁₋₃ alkyl, C₁₋₃ alkoxy, or halo. Withinthis genus, the organic substrate includes substituted 1,2-diols,1,3-diols, 1,4-diols, these being substituted with one or more alkyland/or optionally substituted aryl or heteroaryl substituents. Incertain Aspects of this Embodiment, the organic substrate is any onehaving a terminal olefin as described in U.S. patent application Ser.No. 15/219,710 (alcohols with hydroxides), filed Jul. 26, 2016, which isincorporated by reference herein for all purposes, or at least for theseteachings.

EXAMPLES

The following Examples are provided to illustrate some of the conceptsdescribed within this disclosure. While each Example is considered toprovide specific individual embodiments of composition, methods ofpreparation and use, none of the Examples should be considered to limitthe more general embodiments described herein.

In the following examples, efforts have been made to ensure accuracywith respect to numbers used (e.g. amounts, temperature, etc.) but someexperimental error and deviation should be accounted for. Unlessindicated otherwise, temperature is in degrees C., pressure is at ornear atmospheric.

Example 1: General Information

Unless otherwise stated, reactions were performed in a nitrogen-filledglovebox or in flame-dried glassware under an argon or nitrogenatmosphere using dry, deoxygenated solvents. Solvents were dried bypassage through an activated alumina column under argon. Reactionprogress was monitored by thin-layer chromatography (TLC), GC or Agilent1290 UHPLC-MS. TLC was performed using E. Merck silica gel 60 F254precoated glass plates (0.25 mm) and visualized by UV fluorescencequenching, p-anisaldehyde, or KMnO₄ staining. Silicycle SiliaFlash® P60Academic Silica gel (particle size 40-63 nm) was used for flashchromatography. ¹H NMR spectra were recorded on Varian Inova 500 MHz orBruker 400 MHz spectrometers and are reported relative to residual CHCl₃(δ 7.26 ppm), C₆H₆ (δ 7.16 ppm), or THF (δ 3.58, 1.72 ppm). ¹³C NMRspectra were recorded on a Varian Inova 500 MHz spectrometer (125 MHz)or Bruker 400 MHz spectrometers (100 MHz) and are reported relative toCHCl₃ (δ 77.16 ppm). Data for ¹³C NMR are reported in terms of chemicalshifts (δ ppm). IR spectra were obtained by use of a Perkin ElmerSpectrum BXII spectrometer or Nicolet 6700 FTIR spectrometer using thinfilms deposited on NaCl plates and reported in frequency of absorption(cm⁻¹). GC-FID analyses were obtained on an Agilent 6850N gaschromatograph equipped with a HP-1100% dimethylpolysiloxane capillarycolumn (Agilent). GC-MS analyses were obtained on an Agilent 6850 gaschromatograph equipped with a HP-5 (5%-phenyl)-methylpolysiloxanecapillary column (Agilent). High resolution mass spectra (HRMS) wereobtained from Agilent 6200 Series TOF with an Agilent G1978A Multimodesource in electrospray ionization (ESI+), atmospheric pressure chemicalionization (APCI+), or mixed ionization mode (MM: ESI-APCI+), orobtained from Caltech mass spectrometry laboratory. FT-ATR IRmeasurements were carried out on a Thermo Scientific Nicolet iS 5 FT-IRspectrometer equipped with an iD5 ATR accessory. ReactJR measurementswere carried out on a Mettler-Toledo ReactJR ic10 using a K4 conduitwith a Sentinel high-pressure probe and SIComp window. Electronparamagnetic resonance (EPR) spectra were acquired on a X-band BrukerEMX spectrometer. An Omnical SuperCRC or Insight CPR 220 reactioncalorimeter were used to monitor heat flow.

Triethyl silane (99%, Sure/Seal™) and KOt-Bu (sublimed grade, 99.99%trace metals basis) were purchased from Aldrich and used directly. KOHwas pulverized and dried in a desiccator over P₂O₅ under vacuum for 24 hprior to use. Other reagents were purchased from Sigma-Aldrich, AcrosOrganics, Strem, or Alfa Aesar and used as received unless otherwisestated.

Example 2. Representative Conditions Example 2.1. Reaction Conditions

General reaction procedure: In a nitrogen-filled glovebox, catalyst(KOtBu, 0.5 equiv.) was measured into an oven-dried 2 mL glass vial. Theolefin substrate (1.0 equiv) was then added to the vial. Solvent (DME,dimethoxyethane) to make a 1 M concentration of olefin in DME) andsilane (3.0 equiv) are then added, a Teflon stir-bar is placed into thevial, and the reaction is sealed and stirred for 24-96 h at temperaturesranging from 45-150° C. The reaction was quenched by diluting withdiethyl ether; the solution was filtered through a short plug of silicathen concentrated under reduced pressure. Purification by columnchromatography afforded the pure compounds detailed below. The yield wasdetermined by ¹H NMR or GC-FID analysis of the crude mixture using aninternal standard. Cis-/trans-ratios were determined by NMR or GC-FID.

Example 2.2. General Method for the Screening of Base Catalysts andKinetic Profile

In a nitrogen-filled glove box, 1-methylindole (0.5 mmol, 1 equiv),triethylsilane (1.5 mmol, 3 equiv), the indicated base (0.1 mmol, 20 mol%), and THF (5 mL) were added to a 1 dram vial equipped with a magneticstirring bar. At the indicated time, aliquots were removed using a glasscapillary tube, diluted with Et₂O, and analyzed using GC-FID todetermine regioselectivity and yield. GC conversion is reported asproduct (C2- and C3-silylation) divided by product and startingmaterial. The results are shown in Table 1.

TABLE 1 Results of Evaluating Base Catalysts

entry catalyst Time (h) conv (%) 2:3  1 KOt-Bu 10 88 11:1  2 KOEt 10 55 9:1  3 KOMe 20 35  9:1  4 KOTMS 20 53 12:1  5 KOAc 60 0 —  6 KOH 20 5211:1  7 KH 36 0 —  8 KC₈ 10 73  8:1  9 CsOH•H₂O 10 64  8:1 10 RbOH•xH₂O10 38 10:1 11 LiOt-Bu 36 0 — 12 NaOt-Bu 36 0 — 13 Mg(Ot-Bu)₂ 36 0 — 14Ca(Oi-Pr)₂ 36 0 — 15 Ba(Ot-Bu)₂ 36 0 — 16 Al(Ot-Bu)₃ 36 0 —

Example 2.3. Procedure for Time Course Reaction Monitoring by In Situ ¹HNMR

In a nitrogen-filled glove box, a stock solution containing KOt-Bu (60.5mg, 0.539 mmol) and 1,2,5-trimethoxybenzene (if used, 45.4 mg, 0.267mmol) is prepared in THF-D₈ (2.7 ml). Continuing in the glove box, aJ-Young gas-tight NMR tube is then charged with 1-methylindole (32.8 mg,0.25 mmol, 1 equiv), Et₃SiH (0.75 mmol, 3 equiv), and 0.25 mL of stocksolution. The tube is tightly capped with the corresponding Teflon plug,removed from the glove box, placed in the bore of the NMR, and heated to45° C. ¹H NMR spectra were acquired in “array” mode, with a spectrumtaken approximately every 3 minutes for the length of experiment. Thedata was processed using MestReNova and peak integrations werenormalized to 1,2,5-trimethoxybenzene (if used).

A study was conducted following the procedure for time course reactionmonitoring by ¹H NMR (using internal standard) while varying1-methyl-indole [1], from 0.25-0.76 mmol (0.5-1.5 equiv). A burst phaseof product formation followed an initial induction phase, unfortunatelydue to the induction period it was difficult to assign an initial ratefor this phase but all trials appear to have a similar rate during theburst phase. The length of the burst phase (i.e. product formed) appearsto be related to the nature of the substrate. Interestingly, after theburst phase the slope of all plots appear to be consistent, indicatingthe reaction may not depend on the nature of the substrate. See FIGS. 2and 4. This work helped demonstrate that silylation reaction occurred inthe following 3 regimes; induction, burst, and sustained reactionperiods.

Example 2.4. Procedure for Time Course Reaction Monitoring by GCAnalysis of Reaction Aliquots

In a nitrogen-filled glove box, 1 dram vials with magnetic stirring barswere charged with the indicated base (0.1 mmol, 20 mol %, RbOH suppliedas unknown hydrate from Strem and used as received), 1-methylindole(65.6 mg, 0.5 mmol, 1 equiv), triethylsilane (174.4 mg, 1.5 mmol, 3equiv) and THF (0.5 mL, 1M) then sealed with a PTFE-lined screw-cap andheated to 45° C. while stirring. At the indicated time points, analiquot was removed with a clean, dry glass capillary tube, diluted withEt₂O, and analyzed by GC-FID. Conversion is reported as the percent ofboth C2- and C3-silylation products divided by products and startingmaterial. Regioselectivity (i.e. C2- to C3-silylation ratios, Table 2)were also obtained at each time point.

TABLE 2 Time C2:C3 ratio Base (h) Conversion (x:1) KOt-Bu 1.0 0.0 — 2.00.0 — 3.0 25.8 27.3 4.0 44.2 24.1 5.0 57.4 23.2 6.0 66.5 12.8 8.0 81.416.9 10.0 88.0 15.0 20.0 89.2 15.0 36.0 91.0 9.3 KOTMS 1.0 0.0 — 2.0 0.0— 3.0 0.0 — 4.0 3.9 7.1 5.0 10.2 9.9 6.0 17.7 9.0 8.0 26.2 19.9 10.033.0 14.1 20.0 50.4 11.6 36.0 59.9 9.0 KHMDS 1.0 0.0 — 2.0 0.0 — 3.0 0.0— 4.0 1.2 >20 5.0 2.5 >20 6.0 4.7 9.7 8.0 8.3 15.0 10.0 10.3 11.0 20.021.6 21.5 36.0 34.9 7.3 KOEt 1.0 19.7 — 2.0 24.8 26.8 3.0 30.6 22.3 4.035.7 19.4 5.0 38.5 19.2 6.0 40.9 11.4 8.0 51.1 14.0 10.0 54.9 12.5 20.067.1 8.2 36.0 75.6 6.2 KOMe 1.0 0.0 — 2.0 0.0 — 3.0 0.0 — 4.0 1.2 >205.0 2.5 >20 6.0 5.6 7.0 8.0 15.7 15.4 10.0 24.2 12.3 20.0 35.2 14.9 36.051.5 7.2 KOH 1.0 0.0 — 2.0 0.0 — 3.0 0.0 — 4.0 0.0 — 5.0 0.0 — 6.0 0.0 —8.0 17.8 >20 10.0 34.3 18.4 20.0 49.9 11.3 36.0 63.2 7.0 CsOH 1.02.2 >20 2.0 14.9 21.4 3.0 27.6 23.0 4.0 35.6 20.5 5.0 42.8 19.5 6.0 51.212.1 8.0 57.7 15.2 10.0 64.0 11.6 20.0 73.2 7.7 36.0 74.0 5.8 RbOH 1.00.0 — 2.0 0.0 — 3.0 5.8 5.3 4.0 12.1 10.5 5.0 17.8 18.9 6.0 23.9 19.98.0 30.8 14.1 10.0 37.5 11.0 20.0 48.2 9.5 36.0 59.4 7.9 KC8 1.022.4 >20 2.0 28.0 33.1 3.0 30.6 23.1 4.0 41.4 21.2 5.0 43.7 22.8 6.052.5 14.6 8.0 63.0 14.9 10.0 72.6 8.5 20.0 82.2 7.7 36.0 84.7 5.0

Example 2.5. Procedure for Reaction Time Course Using ReactIR

The glass reaction vessel for use with the ReactIR Sentinelhigh-pressure probe and a magnetic stirring bar were oven dried, fittedwith the PTFE adapter, and brought into a nitrogen-filled glove box, orcooled under a flow of argon and standard air-free technique is used forall additions. KOt-Bu (0.8 mmol, 20 mol %), 1-methylindole (1.05 g, 8mmol, 1 equiv), triethylsilane (13.89 mL, 24 mmol, 3 equiv), additive,and THF (8 mL, 1M) were added to reaction vessel, which was fitted tothe ReactIR probe and heated to 45° C. while stirring under argon. Thespectrum was recorded over the course of the reaction and data wasanalyzed using the ReactIR software. See FIGS. 5 and 6.

An analogous experiment was performed whereby the indole 1 is not addeduntil the new peak attributed to the hypercoordinated silicate is seen.Indole 1 is then added via syringe and the reaction immediately proceedswith no induction period.

Example 2.6. General Procedure of ATR-FTIR Measurement

In a nitrogen-filled glove box, base (0.1 mmol), Et₃SiH (800.5 mmol, 5equiv), and THF (0.5 mL) were added to a 1 dram scintillation vialequipped with a magnetic stirring bar. The vial was sealed and themixture stirred at 45° C. for the indicated time as shown in Table 3.The vial was transferred to another nitrogen-filled glove box with anATR-FTIR and a few drops of this mixture placed on the ATR crystal.After waiting for 5 minutes to evaporate all the volatiles (i.e. THF andsilanes), the IR spectrum of the residue was recorded. No new Si—Hstretch was observed with bases which did not catalyze the silylationreaction (e.g. NaOt-Bu, Mg(Ot-Bu)₂, or LiOt-Bu) as these did not formthe requisite hypercoordinated complex. See Table 3 and FIGS. 7(A)-(O).

TABLE 3 Spectroscopic characterization of the reaction of Et₃Si—H withthe bases evaluation in this study

υ [Si—H] Entry Base [Si]—X t (h)^(a) (cm⁻¹)^(b) Δυ(cm⁻¹)^(c)  1 — Et₃SiH— 2099 —  2 KOt-Bu Et₃SiH 2 2028 71  3 KOEt Et₃SiH 2 2016 83  4 KOMeEt₃SiH 7 2054 45  5 KOTMS Et₃SiH 7 2047 52  6 KOH Et₃SiH 20 2045 54  7RbOH•xH₂O Et₃SiH 7 2052 47  8 CsOH•xH₂O Et₃SiH 7 2051 48  9 NaOt-BuEt₃SiH 36 — — 10 KOt-Bu Et₃SiD 12 — — 11 KOt-Bu Et₃SiH (2.5 equiv) + 122029 70 Et₃SiD(2.5 equiv) 12 Mg(Ot-Bu)₂ Et₃SiH 36 — — 13 LiOt-Bu Et₃SiH36 — — ^(a)The mixture was stirred for the indicated time before IRspectrum was measured. ^(b)Frequency of Si—H bond stretching.^(c)Frequency shift of observed hypercoordinated silicon species fromEt₃Si—H.

Example 2.7. Other Specific, Representative Examples

Trimethylsilane: In a related experiment, directed to investigating theuse of gaseous hydrosilanes, trimethylsilane (Me₃SiH, 15 mmol), KO-tBu(0.076 mmol), and THF (0.38 mL) were added to a Schlenk flask, sealedwith a Teflon stopper, and allowed to sit at RT (˜23° C.) forapproximately 3 weeks. In a N₂ filled glovebox, 1-methyl-indole (0.38mmol) was added and the reaction is heated to 45° C. for 48 hours.¹H-NMR indicated a conversion to 1-methyl-2-trimethylsilyl indole ofapproximately 73%.

Hexamethyldisilane: In another related experiment, directed toinvestigating the use of organodisilanes, hexamethyldisilane (2 mmol),KO-tBu (0.2 mmol), and THF (1 mL) were combined in a sealed vial in anitrogen-filled glovebox and heated to 45° C. for 24 hours. The solutionwas then allowed to cool and 241 mg of this mixture is added to a vialcontaining 1-methyl-indole (0.2 mmol). This vial is sealed and heated to45° C. for 24 hours. ¹H-NMR indicated a conversion to1-methyl-2-trimethylsilyl indole of approximately 76%.

Benzyl alcohol: In a N₂ filled glove box, benzyl alcohol (0.2 mmol, 21.6mg, dried by MgSO₄ and 3 Å MS) was added to a vial. Premixed silylationsolution (251 mg, containing 0.04 mmol KOtBu, 0.6 mmol Et₃SiH, and 0.2mL THF) was added and the solution was heated to 45° C. After 48 h thereaction was removed from heat and a white precipitate was observed. Themixture was quenched with Et₂O when the precipitate went into solution,transferred to a vial, and concentrated in vacuo. The ¹H NMR spectrumshowed full conversion to the product benzyloxytriethylsilylether (alongwith residual silane and a small amount of an unidentified product <0.1by integration).

Deprotecting N-benzoylindole: In a glovebox, a solution was previouslyprepared which contained 3 mmol triethylsilane and 0.2 mmol KOtBu per 1mL THF. This sol was heated to 45° C. for 24 hours then allowed to cooland stored in a glovebox. To 0.2 mmol N-benzoylindole was added 251 mgof the premix sol (containing 0.6 mmol silane, 0.04 mmol KOtBu, and 0.2mL THF) The vial was sealed and heated to 45° C. for 24 hours. Afterdilution with Et₂O, a crude NMR was taken which appeared to show a 1:1of starting material: de-protected indole (i.e., free indole)

Example 3. Discussion

Example 3.1 Effect of Catalyst Identity. The combination of a bulkybasic anion and a potassium cation has previously been reported ascrucial for the C—H silylation of 1-methylindole and otherheteroaromatic substrates. A detailed study of the catalytic competencyof a variety of alkali, alkaline earth, and other metal derived baseshas been conducted. As shown in Table 1, alkoxides and hydroxides ofalkali metals with larger radius cations (i.e. radius ≥K+), such as K⁺,Rb⁺, and Cs⁺ could provide the silylation product in moderate to goodyields (Table 1, entries 1-4, 6, 9 and 10).

Among all the catalysts examined, KOt-Bu was proven to be the idealcatalyst, affording the highest overall yield. However, no product wasdetected when KOAc or KH was employed as the catalyst (entries 5 and 7).Perhaps surprisingly, potassium on graphite (KC8) afforded the desiredproduct in good yield (entry 8). Alkali metal bases with small cations(e.g. LiOt-Bu and NaOt-Bu) demonstrated a complete lack of reactivityand no product was observed even after extended reaction time (entries11 and 12). Alkoxides of alkali earth metals or aluminum were alsoinvestigated as catalysts and failed to afford any product (entries13-16).

The kinetic behavior of the silylation reaction with KOt-Bu catalyst wasstudied using in situ 41 NMR spectroscopy. While not previouslyreported, as depicted in FIGS. 1 and 2, the silylation reaction wasfound to take place in three stages: an induction period (FIG. 1), anactive period (“burst”) with rapid formation of product, and a finalperiod with significantly reduced reaction rate. The timeframes of thesethree stages varied with reaction conditions and reaction components(including hydrosilanes, bases, additives, oxygen, moisture, andsolvent), but the induction period was always observed when theseingredients were added simultaneously, or near simultaneously.

Investigations were then expanded to include each active catalystpresented in Table 1 (FIG. 4). The length of the induction period wasfound to depend on the nature of both metal and counter ion. For anions,the induction period increased in the order of KC8 (shortest)<KOEt<KOt-Bu<KOH (longest). An increase in induction period was observed withdecreasing radius of cations, with CsOH (shortest)<RbOH <KOH (longest).It is worth noting that the induction periods vary based on catalystloading, solvents, and reaction temperature. Additives, oxygen, andmoisture could also have a significant impact on the induction period,generally prolonging the duration of such period. Nevertheless, theinduction period showed good reproducibility for identical reactionssetup at different times. Although the induction period with KOt-Bu isnot the shortest of all catalysts tested (see FIG. 4), this catalystprovides the highest post-initiation turnover frequency and productyield.

Example 3.2. Investigation of Coordinated Silane Species by FTIR Studies

By monitoring the silylation reaction using ReactIR, evidence for theexistence of a new, possibly hypercoordinated silicate species wasfound. As shown in FIGS. 5 and 6, the in situ IR spectrum, a new peak isvisible at 2056 cm′ adjacent to the Si—H stretching band in Et₃SiH (2100cm⁻¹). This lower frequency peak is consistent with an elongated,weakened Si—H axial bond in a five-coordinate silicate, as expected insuch hypercoordinated complexes. A similar shift has been reportedpreviously for the trans Si—H stretching inN,N-dimethylaminopropylsilane [H₃Si(CH₂)₃NMe₂] from 2151 to 2107 cm⁻¹.In this case, the observed redshift was rationalized to occur because ofan N—Si interaction to form a hypercoordinate complex as confirmed byX-ray analysis. In the instant case, a correlation between the newlyformed IR peak (FIG. 5) and the onset of product formation (i.e. theinduction period ending) was observed. Once the new IR peak reached asteady state, the consumption of 1-methylindole 1 and formation ofsilylation product occurred immediately. Furthermore, the new IR peakwas visible throughout the reaction. This is consistent with theobservation that premixing Et₃SiH and KOt-Bu in THF for 2 h at 45° C.followed by the addition of 1-methylindole 1 eliminated the inductionperiod. This is also consistent with the fact that the formation ofhypercoordinated silicate is responsible for the observed inductionperiod.

Further studies were undertaken with mixtures of Et₃SiH and metalalkoxides listed in Table 1 utilizing ATR-FTIR in a nitrogen filledglove box after removal of the volatiles (i.e. THF, Et₃SiH). As shown inFIG. 7(A), any alkoxide base which was a competent silylation catalystdeveloped a lower energy Si—H feature (from 2016-2051 cm′, correspondingto the Si—H bond of a hypercoordinated silicon species. In sharpcontrast, no such species were detected with unreactive catalysts [i.e.,LiOt-Bu, NaOt-Bu (FIGS. 7(M) and 7(N)), alkali earth metals, or aluminumalkoxides] demonstrating that this new optionally solvatedhypercoordinated complex appears to be crucial for the silylationreaction. For the hypercoordinated silicates formed from KOt-Bu andKOEt, the decrease in the frequencies of Si—H absorption correlates to ashortening of induction period (FIGS. 7(D) and 7(E)). Finally, althoughthere is a large variation in the induction periods with KOH, RbOH andCsOH, no differentiating Si—H frequencies of the hypercoordinatedsilicates derived from those bases are observed. The hydroxides areconverted to the silanolates, and subsequently silicates, which serve asthe active catalysts.

As those skilled in the art will appreciate, numerous modifications andvariations of the present invention are possible in light of theseteachings, and all such are contemplated hereby. All references citedwithin this specification are incorporated by reference, at least fortheir teachings in the context of their recitation.

What is claimed:
 1. A method of silylating an organic substrate having aC—H bond or an O—H bond, the method comprising contacting the organicsubstrate with a mixture of: (a) a precursor hydrosilane ororganodisilane; and (b) a base comprising a potassium silanolate, apotassium amide, rubidium hydroxide, a rubidium alkoxide, a rubidiumsilanolate, cesium hydroxide, a cesium alkoxide, a cesium silanolate, agraphitic potassium (KC₈), or a combination thereof; wherein thecontacting results in the formation of a C—Si bond in the positionpreviously occupied by the C—H bond or an O—Si bond in the positionpreviously occupied by the O—H bond, respectively; and wherein the C—Hbond is: (a) located on a heteroaromatic moiety; (b) located on analkyl, alkoxy, or alkylene moiety positioned alpha to an aryl orheteroaryl moiety; (c) an alkynyl C—H bond; or (d) a terminal olefinicC—H bond.
 2. The method of claim 1 wherein the mixture is preconditionedbefore contacting with the organic substrate, the preconditioningcomprising holding the mixture comprising the precursor hydrosilane andthe base at one or more temperatures in a range of from about 25° C. toabout 125° C. for a time in a range of from about 30 minutes to about 24hours.
 3. The method of claim 1, wherein the mixture further comprises asolvent.
 4. The method of claim 3, wherein the solvent istetrahydrofuran or 2-methyltetrahydrofuran.
 5. The method of claim 1,wherein the base comprises rubidium hydroxide, or cesium hydroxide. 6.The method of claim 1, wherein the base comprises a potassium amide. 7.The method of claim 1, wherein the base comprises a rubidium alkoxide,or a cesium alkoxide.
 8. The method of claim 1, wherein the basecomprises a potassium silanoate, a rubidium silanolate, or a cesiumsilanolate.
 9. The method of claim 1, wherein the base comprises agraphitic potassium (KC₈).
 10. The method of claim 1, wherein theprecursor hydrosilane is of the Formula (I) or Formula (II) or theprecursor organodisilane is of the Formula (III):(R)_(3−m)Si(H)_(m+1)  (I)(R)_(3−m)(H)_(m)Si—Si(R)_(2−m)(H)_(m+1)  (II)(R′)₃Si—Si(R′)₃  (III) where: m is independently 0, 1, or 2; and each Rand R′ are independently optionally substituted C₁₋₂₄ alkyl orheteroalkyl, optionally substituted C₂₋₂₄ alkenyl, optionallysubstituted C₂₋₂₄ alkynyl, optionally substituted C₆₋₁₂ aryl, C₃₋₁₂heteroaryl, optionally substituted C₇₋₁₃ alkaryl, optionally substitutedC₄₋₁₂ heteroalkaryl, optionally substituted C₇-13 aralkyl, optionallysubstituted C₄₋₁₂ heteroaralkyl, and, if substituted, the substituentsmay be phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C₁-C₂₀ alkylsulfinyl, 5 to 12 ring-membered arylsulfinyl,sulfonamido, amino, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy,C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl,silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or ametal-containing or metalloid-containing group, where the metalloid isSn or Ge, where the substituents may optionally provide a tether to aninsoluble or sparingly soluble support media comprising alumina, silica,or carbon.
 11. The method of claim 1, wherein the at least onehydrosilane is (R)₃SiH or (R)₂SiH₂, where R is independently at eachoccurrence C₁₋₆ alkyl, phenyl, tolyl, or pyridinyl.
 12. The method ofclaim 1, wherein the organic substrate contains an —OH bond and thecontacting results in the formation of an O—Si bond in the positionpreviously occupied by the O—H bond.
 13. The method of claim 1, whereinthe organic substrate contains a C—H bond, wherein the C—H bond is: (a)located on the heteroaromatic moiety; or (b) located on an alkyl,alkoxy, or alkylene moiety positioned alpha to an aryl or heteroarylmoiety; and the contacting results in the formation of a C—Si bond inthe position previously occupied by the C—H bond.
 14. The method ofclaim 1, wherein the organic substrate contains a C—H bond, wherein theC—H bond is an alkynyl C—H bond and the contacting results in theformation of a C—Si bond in the position previously occupied by the C—Hbond.
 15. The method of claim 1, wherein the organic substrate containsa C—H bond, wherein the C—H bond is a terminal olefinic C—H bond and thecontacting results in the formation of a C—Si bond in the positionpreviously occupied by the C—H bond.